Durable high strength polymer composites suitable for implant and articles produced therefrom

ABSTRACT

Thin, biocompatible, high-strength, composite materials are disclosed that are suitable for use in a valve for regulating blood flow direction. In one aspect, the composite material maintains flexibility in high-cycle flexural applications, making it particularly applicable to high-flex implants such as a prosthetic heart valve leaflet. The composite material includes a porous polymer membrane and an elastomer, wherein the elastomer fills substantially all of the pores of the porous polymer membrane.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of co-pendingU.S. patent application Ser. No. 13/078,774 filed Apr. 1, 2011, which isherein incorporated by reference in its entirety.

FIELD

The invention relates to materials used in medical implants. Moreparticularly, the invention relates to a biocompatible material suitablefor use in high-cycle flexural applications including artificial heartvalves.

BACKGROUND

Artificial heart valves preferably should last at least ten years invivo. To last that long, artificial heart valves should exhibitsufficient durability for at least four hundred million cycles or more.The valves, and more specifically heart valve leaflets, must resiststructural degradation including the formation of holes, tears, and thelike as well as adverse biological consequences including calcificationand thrombosis.

A variety of polymeric materials has previously been employed asprosthetic heart valve leaflets. Failure of these leaflets due tostiffening and hole formation occurred within two years of implant.Efforts to improve leaflet durability by thickening the leafletsresulted in unacceptable hemodynamic performance of the valves, that is,the pressure drop across the open valve was too high.

As such, it remains desirable to provide a biocompatible artificialheart valve design that lasts beyond ten years in vivo by exhibitingsufficient durability for at least about four hundred million cycles offlexure or more.

SUMMARY

According to an embodiment, a valve is provided for regulating bloodflow direction. In an embodiment, the valve includes a leafletcomprising a composite material with at least one synthetic polymermembrane comprising fibers wherein a diameter of the majority of thefibers is less than about 1 μm, the space between the fibers definingpores, the elastomer being disposed in substantially all of the pores.

In another embodiment, the valve includes a support structure and atleast one leaflet being supported on the support structure and movablebetween open and closed positions. Each leaflet includes a compositematerial comprising at least one synthetic polymer membrane and anelastomer. The at least one synthetic polymer membrane comprises fiberswherein a diameter of the majority of the fibers is less than about 1μm. The space between the fibers define pores. The elastomer is disposedin substantially all of the pores.

In another embodiment, the valve includes a support structure and atleast one leaflet supported on the support structure and movable betweenopen and closed positions. Each leaflet includes a composite materialcomprising at least one synthetic polymer membrane and an elastomer. Theat least one synthetic polymer membrane comprises pores with theelastomer present in substantially all of the pores. The compositematerial comprises synthetic polymer membrane by weight in the range ofabout 10% to 90%.

In another embodiment, the valve includes a support structure and atleast one leaflet supported on the support structure and movable betweenopen and closed positions. Each leaflet includes a composite materialcomprising at least one synthetic polymer membrane and an elastomer. Theat least one synthetic polymer membrane comprises pores having a poresize less than about 5 μm with the elastomer present in substantiallyall of the pores.

In another embodiment, a method of forming a leaflet of a prostheticheart valve is provided. The method comprises providing a compositematerial comprising at least one synthetic polymer membrane and anelastomer, the at least one synthetic polymer membrane comprising fiberswherein a diameter of the majority of the fibers is less than about 1μm, the space between the fibers defining pores, the elastomer beingdisposed in substantially all of the pores; bringing more than one layerof the composite material into contact with additional layers of thecomposite material; and bonding the layers of composite materialtogether.

In another embodiment, a method of forming a prosthetic heart valveincluding leaflets is provided. The method comprises: providing agenerally annular support structure; providing a composite materialcomprising at least one synthetic polymer membrane and an elastomer, theat least one synthetic polymer membrane comprising fibers wherein adiameter of the majority of the fibers is less than about 1 μm, thespace between the fibers defining pores, the elastomer being disposed insubstantially all of the pores; wrapping the composite material aboutthe support structure bringing more than one layer of the compositematerial into contact with additional layers of the composite material;and bonding the layers of composite material to itself and to thesupport structure.

In another embodiment, a method of forming a leaflet of a prostheticheart valve is provided. The method comprises providing a compositematerial comprising at least one synthetic polymer membrane and anelastomer, the at least one synthetic polymer membrane comprisingfibers, the space between the fibers defining pores that have a poresize of less than about 5 μm, the elastomer being disposed insubstantially all of the pores; bringing more than one layer of thecomposite material into contact with additional layers of the compositematerial; and bonding the layers of composite material together.

In another embodiment, a method of forming a prosthetic heart valveincluding leaflets is provided. The method comprises: providing agenerally annular support structure; providing a composite materialcomprising at least one synthetic polymer membrane and an elastomer, theat least one synthetic polymer membrane comprising fibers, the spacebetween the fibers defining pores that have a pore size of less thanabout 5 μm, the elastomer being disposed in substantially all of thepores; wrapping the composite material about the support structurebringing more than one layer of the composite material into contact withadditional layers of the composite material; and bonding the layers ofcomposite material to itself and to the support structure.

In another embodiment, the valve includes a generally annular shapedsupport structure having a first end and a second end opposite the firstend. The second end comprises a plurality of posts extendinglongitudinally therefrom. A sheet of composite material extends frompost to post wherein leaflets are defined by the composite material thatis between the posts. In an embodiment, a cushion member is coupled tothe post and provides a cushion between the post and the leaflets tominimize stress and wear on the leaflets as the leaflets cycle betweenopen and closed positions.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are included to provide a furtherunderstanding of the invention and are incorporated in and constitute apart of this specification, illustrate embodiments of the invention, andtogether with the description serve to explain the principles of theinvention.

FIGS. 1A, 1B, 1C, and 1D are front, side and top elevational views, anda perspective view, respectively, of a tool for forming a heart valveleaflet, in accordance with an embodiment;

FIG. 2A is a perspective view of a cushion pad being stretched over aleaflet tool, in accordance with an embodiment;

FIG. 2B is a perspective view of a release layer being stretched overthe cushion pad covered leaflet tool in FIG. 2A, in accordance with anembodiment;

FIGS. 3A, 3B and 3C are top, side and front elevational views,respectively, illustrating a step in the formation of a valve leaflet,in which the leaflet tool covered by the cushion pad and release layer(shown in FIGS. 2A and 2B, respectively) is positioned over a compositematerial for cutting and further assembly, in accordance with anembodiment;

FIG. 4 is a top elevational view of a tri-leaflet assembly prior tocutting excess leaflet material, in accordance with an embodiment;

FIG. 5A is a perspective view of the tri-leaflet assembly and a basetool, in accordance with an embodiment;

FIG. 5B is a perspective view of the tri-leaflet assembly and base toolaligned and assembled to form a base tool assembly, in accordance withan embodiment;

FIG. 6A is a flattened plane view of a stent frame or support structure,in accordance with an embodiment;

FIG. 6B is a flattened plane view of the support structure covered in apolymer coating, in accordance with an embodiment;

FIGS. 7A, 7B and 7C are scanning electron micrograph images of expandedfluoropolymer membranes used to form the valve leaflets, in accordancewith an embodiment;

FIG. 8 is a perspective view of a valve assembly, in accordance with anembodiment;

FIGS. 9A and 9B are top elevational views of the heart valve assembly ofFIG. 8 shown illustratively in closed and open positions, respectively,in accordance with an embodiment;

FIG. 10 is a graph of measured outputs from a heart flow pulseduplicator system used for measuring performance of the valve assembliesmade in accordance with embodiments;

FIGS. 11A and 11B are a graph and data chart, respectively, of measuredoutputs from a high rate fatigue tester used for measuring performanceof the valve assemblies made in accordance with embodiments;

FIGS. 12A and 12B are graphs of measured outputs from the heart flowpulse duplicator system taken while testing valve assemblies accordingto embodiments at zero cycles and after about 207 million cycles,respectively;

FIGS. 13A and 13B are graphs of measured outputs from the heart flowpulse duplicator system taken while testing valve assemblies made inaccordance with embodiments at about 79 million cycles and after about198 million cycles, respectively;

FIG. 14 is a perspective view of a mandrel for manufacturing a heartvalve assembly, in accordance with an embodiment;

FIG. 15 is a perspective view of a valve frame for a heart valve, inaccordance with an embodiment;

FIG. 16 is a perspective view of the valve frame of FIG. 15 nestedtogether with the mandrel FIG. 14, in accordance with an embodiment;

FIG. 17 is a perspective view of a molded valve, in accordance with anembodiment;

FIG. 18 is a perspective view of a molded valve, showing an attachmentmember for reinforcing a bond between adjacent valve leaflets and a postof a valve frame, in accordance with an embodiment;

FIG. 19 is a perspective view of a valve frame, in accordance with anembodiment;

FIG. 20 is a perspective view of the valve frame of FIG. 19 with poststhat are cushion-wrapped, in accordance with an embodiment;

FIG. 21 is a perspective view of a stereo lithography-formed mandrel, inaccordance with an embodiment;

FIG. 22 is a perspective view of the cushion-wrapped valve frame of FIG.20 mounted onto the mandrel of FIG. 21, in accordance with anembodiment; and

FIG. 23 is a perspective view of a valve having valve leaflets coupledto and supported on the cushion-wrapped valve frame of FIG. 20, inaccordance with an embodiment;

FIG. 24 is a perspective view of a valve frame, in accordance with anembodiment;

FIG. 25 is a perspective view of a valve frame with a cushion layer, inaccordance with an embodiment;

FIG. 26 is a perspective view of a mandrel, in accordance with anembodiment;

FIG. 27 is a perspective view of a valve assembly, in accordance with anembodiment;

FIG. 28 is a perspective view of a mandrel, in accordance with anembodiment;

FIG. 29 is a perspective view of a valve, in accordance with anembodiment;

FIG. 30A is a scanning electron micrograph image of the surface of themicroporous polyethylene membrane used to form the valve leaflets, inaccordance with an embodiment;

FIG. 30B is a scanning electron micrograph image of a cross-section ofthe microporous polyethylene membrane of FIG. 30B, in accordance with anembodiment;

FIG. 31A is a scanning electron micrograph image of stretchedmicroporous polyethylene membrane used to form the valve leaflets, inaccordance with an embodiment; and

FIG. 31B is a scanning electron micrograph image of a cross-section ofthe microporous polyethylene membrane of FIG. 31B, in accordance with anembodiment.

DETAILED DESCRIPTION

References will now be made to embodiments illustrated in the drawingsand specific language which will be used to describe the same. It willnevertheless be understood that no limitation of the scope of theinvention is thereby intended, such alterations and furthermodifications in the illustrated methods and apparatus, as such furtherapplications of the principles of the invention as illustrated thereinas being contemplated as would normally occur to one skilled in the artto which the invention relates.

Definitions for some terms used herein are provided below in theAppendix.

The present disclosure addresses a long-felt need for a material thatmeets the durability and biocompatibility requirements of high-cycleflexural implant applications, such as heart valve leaflets. It has beenobserved that heart valve leaflets formed from porous fluoropolymermaterials or, more particularly, from ePTFE containing no elastomersuffer from stiffening in high-cycle flex testing and animalimplantation.

In one embodiment, described in greater detail below, the flexuraldurability of porous polymer heart valve leaflets was significantlyincreased by adding a relatively high-percentage of relatively lowerstrength elastomer to the pores. Optionally, additional layers of theelastomer may be added between the composite layers. Surprisingly, inembodiments wherein porous polymer membranes are imbibed with elastomerthe presence of the elastomer increased overall thickness of theleaflet, the resulting increased thickness of the polymer members due tothe addition of the elastomer did not hinder or diminish flexuraldurability. Further, after reaching a minimum percent by weight ofelastomer, it was found that fluoropolymer members performed better withincreasing percentages of elastomer resulting in significantly increasedcycle lives exceeding 40 million cycles in vitro, as well as by showingno signs of calcification under certain controlled laboratoryconditions.

A material according to one embodiment includes a composite materialcomprising an expanded fluoropolymer membrane and an elastomericmaterial. It should be readily appreciated that multiple types offluoropolymer membranes and multiple types of elastomeric materials canbe combined while within the spirit of the present invention. It shouldalso be readily appreciated that the elastomeric material can includemultiple elastomers, multiple types of non-elastomeric components, suchas inorganic fillers, therapeutic agents, radiopaque markers, and thelike while within the spirit of the present invention.

In some embodiments, the composite material includes an expandedfluoropolymer material made from porous ePTFE membrane, for instance asgenerally described in U.S. Pat. No. 7,306,729. In some otherembodiments, the composite material includes a polyethylene materialmade from porous polyethylene membrane.

The expandable fluoropolymer, used to form the expanded fluoropolymermaterial described in embodiments, may comprise PTFE homopolymer. Inalternative embodiments, blends of PTFE, expandable modified PTFE and/orexpanded copolymers of PTFE may be used. Non-limiting examples ofsuitable fluoropolymer materials are described in, for example, U.S.Pat. No. 5,708,044, to Branca, U.S. Pat. No. 6,541,589, to Baillie, U.S.Pat. No. 7,531,611, to Sabol et al., U.S. patent application Ser. No.11/906,877, to Ford, and U.S. patent application Ser. No. 12/410,050, toXu et al.

The expanded fluoropolymer in accordance with some embodiments, maycomprise any suitable microstructure for achieving the desired leafletperformance. In one embodiment, the expanded fluoropolymer may comprisea microstructure of nodes interconnected by fibrils, such as describedin U.S. Pat. No. 3,953,566 to Gore. In one embodiment, themicrostructure of an expanded fluoropolymer membrane comprises nodesinterconnected by fibrils as shown in the scanning electron micrographimage in FIG. 7A. The fibrils extend from the nodes in a plurality ofdirections, and the membrane has a generally homogeneous structure.Membranes having this microstructure may exhibit a ratio of matrixtensile strength in two orthogonal directions of less than about 2, andpossibly less than about 1.5.

In another embodiment, the expanded fluoropolymer may have amicrostructure of substantially only fibrils, such as, for example,depicted in FIGS. 7B and 7C, as is generally taught by U.S. Pat. No.7,306,729, to Bacino. FIG. 7C is a higher magnification of the expandedfluoropolymer membrane shown in FIG. 7B, and more clearly shows thehomogeneous microstructure having substantially only fibrils. Theexpanded fluoropolymer membrane having substantially only fibrils asdepicted in FIGS. 7B and 7C, may possess a high surface area, such asgreater than about 20 m²/g, or greater than about 25 m²/g, and in someembodiments may provide a highly balanced strength material having aproduct of matrix tensile strengths in two orthogonal directions of atleast 1.5×10⁵ MPa², and/or a ratio of matrix tensile strengths in twoorthogonal directions of less than about 2, and possibly less than about1.5. It is anticipated that expanded fluoropolymer membrane may have amean flow pore sizes of less than about 5 μm, less than about 1 μm, andless than about 0.10 μm, in accordance with embodiments.

The expanded fluoropolymer in accordance with some embodiments may betailored to have any suitable thickness and mass to achieve the desiredleaflet performance. In some cases, it may be desirable to use a verythin expanded fluoropolymer membrane having a thickness less than about1.0 μm. In other embodiments, it may be desirable to use an expandedfluoropolymer membrane having a thickness greater than about 0.1 μm andless than about 20 μm. The expanded fluoropolymer membranes can possessa specific mass less than about 1 g/m² to greater than about 50 g/m².

Membranes comprising expanded fluoropolymer according to an embodimentcan have matrix tensile strengths ranging from about 50 MPa to about 400MPa or greater, based on a density of about 2.2 g/cm³ for PTFE.

Additional materials may be incorporated into the pores or within thematerial of the membranes or in between the layers of the membranes toenhance desired properties of the leaflet. Composites according to oneembodiment can include fluoropolymer membranes having thicknessesranging from about 500 μm to less than about 0.3 μm.

Embodiments of expanded fluoropolymer membrane combined with elastomerprovides performance attributes required for use in high-cycle flexuralimplant applications, such as heart valve leaflets, in at least severalsignificant ways. For example, the addition of the elastomer improvesthe fatigue performance of the leaflet by eliminating or reducing thestiffening observed with ePTFE-only materials. In addition, it reducesthe likelihood that the material will undergo permanent set deformation,such as wrinkling or creasing, that could result in compromisedperformance. In one embodiment, the elastomer occupies substantially allof the pore volume or space within the porous structure of the expandedfluoropolymer membrane. In another embodiment the elastomer is presentin substantially all of the pores of the at least one fluoropolymerlayer. Having elastomer filling the pore volume or present insubstantially all of the pores reduces the space in which foreignmaterials can be undesirably incorporated into the composite. An exampleof such foreign material is calcium. If calcium becomes incorporatedinto the composite material, as used in a heart valve leaflet, forexample, mechanical damage can occur during cycling, thus leading to theformation of holes in the leaflet and degradation in hemodynamics.

In one embodiment, the elastomer that is combined with the ePTFE is athermoplastic copolymer of tetrafluoroethylene (TFE) and perfluoromethylvinyl ether (PMVE), such as described in U.S. Pat. No. 7,462,675. Asdiscussed above, the elastomer is combined with the expandedfluoropolymer membrane such that the elastomer occupies substantiallyall of the void space or pores within the expanded fluoropolymermembrane. This filling of the pores of the expanded fluoropolymermembrane with elastomer can be performed by a variety of methods. In oneembodiment, a method of filling the pores of the expanded fluoropolymermembrane includes the steps of dissolving the elastomer in a solventsuitable to create a solution with a viscosity and surface tension thatis appropriate to partially or fully flow into the pores of the expandedfluoropolymer membrane and allow the solvent to evaporate, leaving thefiller behind.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of delivering the filler via adispersion to partially or fully fill the pores of the expandedfluoropolymer membrane;

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of bringing the porousexpanded fluoropolymer membrane into contact with a sheet of theelastomer under conditions of heat and/or pressure that allow elastomerto flow into the pores of the expanded fluoropolymer membrane.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of polymerizing the elastomerwithin the pores of the expanded fluoropolymer membrane by first fillingthe pores with a prepolymer of the elastomer and then at least partiallycuring the elastomer.

After reaching a minimum percent by weight of elastomer, the leafletsconstructed from fluoropolymer materials or ePTFE generally performedbetter with increasing percentages of elastomer resulting insignificantly increased cycle lives. In one embodiment, the elastomercombined with the ePTFE is a thermoplastic copolymer oftetrafluoroethylene and perfluoromethyl vinyl ether, such as describedin U.S. Pat. No. 7,462,675, and other references that would be known tothose of skill in the art. For instance, in another embodiment shown inExample 1, a leaflet was formed from a composite of 53% by weight ofelastomer to ePTFE and was subjected to cycle testing. Some stiffeningwas observed by around 200 million test cycles, though with only modesteffect on hydrodynamics. When the weight percent of elastomer was raisedto about 83% by weight, as in the embodiment of Example 2, no stiffeningor negative changes in hydrodynamics were observed at about 200 millioncycles. In contrast, with non-composite leaflets, i.e. all ePTFE with noelastomer, as in the Comparative Example B, severe stiffening wasapparent by 40 million test cycles. As demonstrated by these examples,the durability of porous fluoropolymer members can be significantlyincreased by adding a relatively high-percentage of relatively lowerstrength elastomer to the pores of the fluoropolymer members. The highmaterial strength of the fluoropolymer membranes also permits specificconfigurations to be very thin.

Other biocompatible polymers which may be suitable for use may include,but not be limited to, the groups of urethanes, silicones(organopolysiloxanes), copolymers of silicon-urethane,styrene/isobutylene copolymers, polyisobutylene,polyethylene-co-poly(vinyl acetate), polyester copolymers, nyloncopolymers, fluorinated hydrocarbon polymers and copolymers or mixturesof each of the foregoing.

In addition to expanded fluoropolymer, other biocompatible syntheticpolymers may be suitable for use as a porous membrane. As providedbelow, embodiments comprising microporous polyethylene are provided as abiocompatible polymer suitable for the particular purpose.

An embodiment of a microporous polyethylene membrane includes a sheet ofmaterial comprising substantially all fibers having a diameter of lessthan about 1 μm. In another embodiment of a microporous polyethylenemembrane includes a sheet of non-woven material comprising substantiallyall fibers having a diameter of less than about 1 μm. In some cases, itmay be desirable to use a very thin microporous polyethylene membranehaving a thickness less than about 10.0 μm. In other embodiments, it maybe desirable to use a microporous polyethylene membrane having athickness less than about 0.6 μm.

It is appreciated that the structure of the microporous membranesdisclosed in embodiments provided herein, may be differentiated fromother structures such as fabrics, knits and fiber windings, by lookingat the specific surface area of the material. Embodiments of microporousmembranes provided herein have a specific surface area of greater thanabout 4.0 m²/cc. In accordance with other embodiments of microporousmembranes provided herein have a specific surface area of greater thanabout 10.0 m²/cc. The embodiments provided herein appreciate that amembrane having a specific surface area of greater than about 4.0 tomore than about 60 m²/cc provide a significant improvement to, at least,but not limited to, the durability and lifetime of the heart valve whenused as leaflet material.

It is appreciated that microporous membranes disclosed in embodimentsprovided herein may alternatively be differentiated from otherstructures such as fabrics, knits and fiber windings, by looking at thefiber diameter of the material. Embodiments of microporous membranesprovided herein contain a majority of fibers having a diameter that isless than about 1 μm. Other embodiments of microporous membranesprovided herein contain a majority of fibers having a diameter that isless than about 0.1 μm. The embodiments provided herein recognize that amembrane comprising fibers the majority of which are less than about 1to beyond less than about 0.1 μm provide a significant improvement to,at least, but not limited to, the durability and lifetime of the heartvalve when used as leaflet material.

The microporous polymer membranes of embodiments may comprise anysuitable microstructure and polymer for achieving the desired leafletperformance. In some embodiments, the microporous polymer membrane isporous polyethylene that has a microstructure of substantially onlyfibers, such as, for example, depicted in FIGS. 30A and 30B for thematerial included in Example 4 and FIGS. 31A and 31B for the materialincluded in Example 5. FIG. 30 shows a substantially homogeneousmicrostructure of the porous polyethylene membrane having substantiallyonly fibers having a diameter of less than about 1 μm. The porouspolyethylene membrane had a thickness of 0.010 mm, a porosity of 31.7%,a mass/area of 6.42 g/m², and a specific surface area of 28.7 m²/cc.

FIGS. 31A and 31B, a surface and cross-sectional view, respectively, isthe same porous polyethylene membrane shown in FIGS. 30A and 30B, asurface and cross-sectional view, respectively, that has been stretchedin accordance with a process described below for Example 5. Thestretched polyethylene membrane retains a substantially homogeneousmicrostructure having substantially only fibers having a diameter ofless than about 1 μm. The stretched polyethylene membrane had athickness of 0.006 mm, a porosity of 44.3%, a mass/area of 3.14 g/m²,and a specific surface area of 18.3 m²/cc. It is anticipated thatmicroporous polyethylene membrane may have a mean flow pore sizes ofless than about 5 μm, less than about 1 μm, and less than about 0.10 μm,in accordance with embodiments.

The following non-limiting examples are provided to further illustratevarious embodiments.

Example 1

In accordance with an embodiment, heart valve leaflets were formed froma composite material having an expanded fluoropolymer membrane and anelastomeric material and joined to a metallic balloon expandable stent,as described by the following embodiment of a process:

A thick, sacrificial tooling cushion pad or layer was formed by foldinga ePTFE layer over upon itself to create a total of four layers. TheePTFE layer was about 5 cm (2″) wide, about 0.5 mm (0.02″) thick and hada high degree of compressibility, forming a cushion pad. Referring toFIGS. 1 and 2, the cushion pad 200 was then stretched (FIG. 2) onto aleaflet tool, generally indicated at 100. The leaflet tool 100 has aleaflet portion 102, a body portion 104 and a bottom end 106. Theleaflet portion 102 of the leaflet tool 100 has a generally arcuate,convex end surface 103. The cushion pad 200 was stretched and smoothedover the end surface 103 of the leaflet portion 102 of the leaflet tool100 by forcing the leaflet tool 100 in the direction depicted by thearrow (FIG. 2A). A peripheral edge 202 of the cushion pad 200 wasstretched over the bottom end 106 of the leaflet tool 100 and twisted tohold the cushion pad 200 in place (FIG. 2B).

Referring to FIG. 2B, a release layer 204 was then stretched over theleaflet portion 102 of the leaflet tool 100 which in the previous stepwas covered with the cushion pad 200. In one embodiment, the releaselayer 204 was made from a substantially nonporous ePTFE having a layerof fluorinated ethylene propylene (FEP) disposed along an outer surfaceor side thereof. The release layer 204 was stretched over the leaflettool 100 such that the FEP layer faced toward the cushion pad 200 andthe substantially nonporous ePTFE faced outwardly or away from thecushion pad 200. The release layer was about 25 μm thick and ofsufficient length and width to allow the release layer 204 to be pulledover the bottom end 106 of the leaflet tool 100. As with the cushion pad200 in the previous step, a peripheral edge 206 of the release layer 204was pulled toward the bottom end 106 of the leaflet tool 100 and thentwisted onto the bottom end 106 of the leaflet tool 100 to retain orhold the release layer 204 in place. The FEP layer of the release layer204 was then spot-melted and thereby fixedly secured to the cushion pad200, as required, by the use of a hot soldering iron.

The processes of Steps 1) and 2) were repeated to prepare three separateleaflet tools, each having a cushion pad covered by a release layer.

A leaflet material according to one embodiment was formed from acomposite material comprising a membrane of ePTFE imbibed with afluoroelastomer. A piece of the composite material approximately 10 cmwide was wrapped onto a circular mandrel to form a tube. The compositematerial was comprised of three layers: two outer layers of ePTFE and aninner layer of a fluoroelastomer disposed therebetween. The ePTFEmembrane was manufactured according to the general teachings describedin U.S. Pat. No. 7,306,729. The fluoroelastomer was formulated accordingto the general teachings described in U.S. Pat. No. 7,462,675.Additional fluoroelastomers may be suitable and are described in U.S.Publication No. 2004/0024448.

The ePTFE membrane had the following properties: thickness=about 15 μm;MTS in the highest strength direction=about 400 MPa; MTS strength in theorthogonal direction=about 250 MPa; Density=about 0.34 g/cm³; IBP=about660 KPa.

The copolymer consists essentially of between about 65 and 70 weightpercent perfluoromethyl vinyl ether and complementally about 35 and 30weight percent tetrafluoroethylene.

The percent weight of the fluoroelastomer relative to the ePTFE wasabout 53%_(.)

The multi-layered composite had the following properties: thickness ofabout 40 μm; density of about 1.2 g/cm³; force to break/width in thehighest strength direction=about 0.953 kg/cm; tensile strength in thehighest strength direction=about 23.5 MPa (3,400 psi); force tobreak/width in the orthogonal direction=about 0.87 kg/cm; tensilestrength in the orthogonal direction=about 21.4 MPa (3100 psi), IPAbubble point greater than about 12.3 MPa, Gurley Number greater thanabout 1,800 seconds, and mass/area=about 14 g/m².

The following test methods were used to characterize the ePTFE layersand the multi-layered composite.

The thickness was measured with a Mutitoyo Snap Gage Absolute, 12.7 mm(0.50″) diameter foot, Model ID-C112E, Serial #10299, made in Japan. Thedensity was determined by a weight/volume calculation using anAnalytical Balance Mettler PM400 New Jersey, USA. The force to break andtensile strengths were measured using an Instron Model #5500R Norwood,Mass., load cell 50 kg, gage length=25.4 cm, crosshead speed=25mm/minute (strain rate=100% per minute) with flat faced jaws. The IPABubble Point was measured by an IPA bubble point tester, PressureRegulator Industrial Data Systems Model LG-APOK, Salt Lake City, Utah,USA, with a Ramp Rate of 1.38 KPa/s (0.2 psi/s), 3.14 cm² test area. TheGurley Number was determined as the time in seconds for 100 cm³ of airto flow through a 6.45 cm² sample at 124 mm of water pressure using aGurley Tester, Model #4110, Troy, N.Y., USA.

Unless otherwise noted, these test methods were used to generate thedata in subsequent examples.

Layers of the composite material, each having two outer layers of ePTFEand an inner layer of a fluoroelastomer disposed therebetween, waswrapped onto a mandrel having a diameter of about 28 mm (1.1″) such thatthe higher strength direction of the membrane was oriented in the axialdirection of the mandrel. In one embodiment, four layers of thecomposite material were wrapped in a non-helical, generallycircumferential fashion onto the mandrel. The composite material had aslight degree of tackiness that allowed the material to adhere toitself. While still on the mandrel, the composite material was slitlongitudinally generally along the mandrel long axis to form a sheetabout 10 cm (4″) by about 90 mm (3.5″).

The resulting sheet of leaflet material (or composite material from Step4) was then cut and wrapped onto the leaflet tool 100 having a cushionpad 200 covered by a release layer 204. More specifically, as shown inFIGS. 3A-3C, the leaflet material 300 was placed onto a flat cuttingsurface. The leaflet tool 100 with the cushion pad 200 and release layer204 was then aligned onto the leaflet material 300 approximately asshown. Four slits 302, 304, 306, 308 were then formed in the leafletmaterial 300 with a razor blade. One pair of slits 302, 304 extends fromone side of the leaflet tool 100 and terminates at one edge 300 a of theleaflet material 300, and the other pair of slits 306, 308 extends froman opposite side of the leaflet tool 100 and terminates at an oppositeedge 300 b of the leaflet material 300. The slits 302, 304, 306, 308were spaced apart from the leaflet portion 102 of the leaflet tool 100.The slits 302, 304, 306, 308 did not protrude under the leaflet tool100. It should be appreciated that the widths of the individual slitsare shown not to scale. The slits 302, 304, 306, 308 in the leafletmaterial 300 resulted in the formation of a folding portion 310, a pairof straps 312, 314 and excess material of leaflet material 315. Thefolding portions 310 were then folded in the general direction indicatedby the arrows 316 in FIG. 3C and smoothed over the leaflet tool 100,which was covered by the cushion pad 200 and the release layer 204 inthe previous steps.

The leaflet material 315 was then stretched and smoothed over theleaflet portion 102, particularly the end surface 103 of the leaflettool 100. The Steps 4) and 5) were repeated to form three separateleaflet assemblies. The three leaflet assemblies 402, 404, 406 were thenclamped together to form a tri-leaflet assembly 400, as shown in FIG. 4.Shown are the three separate leaflet assemblies 402, 404, 406, eachhaving an excess material of leaflet material 315 extending generallyradially beyond the periphery of the tri-leaflet assembly 400.

A base tool was then provided having cavities for engaging the endsurfaces of the leaflet tools of the tri-leaflet assembly and trimmingthe excess leaflet area to form three leaflets. Referring to FIG. 5A,the base tool is generally indicated at 500 and extends longitudinallybetween an end 501 and an opposite bottom end 503. Three concavecavities 502, 504, 506 are formed in the end 501 of the base tool 500.Each concave cavity 502, 504, 506 is formed to match fit or nestinglyseat the end surface 103 of one of the three leaflet assemblies 402,404, 406. Three radially extending elements 508, 510, 512 extendoutwardly from the end of the base tool 500. Each element 508, 510, 512is disposed between an adjacent pair of concave cavities 502, 504, 506.

The base tool 500 was then prepared having a compression pad and arelease layer (not shown) similar to how the leaflet tool was preparedin Steps 1 and 2. As described for each leaflet tool in Steps 1 and 2,the compression pad and the release layer were similarly stretched andaffixed to the base tool 500 to form a base tool assembly.

Referring to FIG. 5B, the base tool assembly (illustrated forconvenience as the base tool 500 without showing the cushion pad and therelease layer) and the tri-leaflet assembly, generally indicated at 400,were then generally axially aligned together so that the end surface(not shown) of each leaflet tool 100 was seated into one of the concavecavities (not shown) in the end 501 of the base tool, generallyindicated at 500, to form a combined tool assembly.

A metallic balloon expandable stent was then fabricated. A tube of 316stainless steel having a wall thickness of about 0.5 mm (0.020″) and adiameter of about 2.5 cm (1.0″) was laser cut. A pattern was cut intothe tube to form an annular-shaped cut stent frame or support structure,which is generally indicated at 600 and shown illustratively in a flat,plane view in FIG. 6 a. The support structure 600, includes a pluralityof small closed cells 602, a plurality of large closed cells 604, and aplurality of leaflet closed cells 606. Note that one of the plurality ofleaflet closed cells 606 appears as an open cell in FIG. 6A due to theflat plane view. The cells 602, 604, 606 are generally arranged alongrows forming the annular shape of the support structure 600.

Polymeric materials were then adhered to the laser cut stent frame.First, a sacrificial compression layer of ePTFE membrane was wrappedwithout overlap onto a mandrel (not shown) having a diameter of about2.5 cm (1.0″). The sacrificial compression layer of ePTFE membrane had athickness of about 0.5 mm (0.02″) and a width of about 10 cm (4″), andwas compliant and compressible to provide a soft, sacrificialcompression layer.

Four layers of a substantially nonporous, ePTFE film were then wrappedonto the mandrel on top of the compression layer membrane. Thesubstantially nonporous, ePTFE film had a thickness of about 25 μm(0.001″), was about 10 cm (4″) wide and had a layer of FEP on one side.The substantially nonporous, ePTFE film was wrapped with the FEP facingaway from the mandrel. The substantially nonporous, ePTFE film had theproperties of the release layer previously described in Step 2).

A thin film of type 1 (ASTM D3368) FEP was constructed using meltextrusion and stretching. An additional 10 layers of this type 1 (ASTMD3368) FEP film was added to the mandrel, which was previously wrappedin the compression layer membrane in Step 10 and the four layers ofsubstantially nonporous, ePTFE film in Step 11. The type 1 (ASTM D3368)FEP film was about 40 μm (0.0016″) thick and was about 7.7 cm (3″) wide.

The wrapped mandrel was then heat treated in an air convection oven atabout 320° C. for about 5 minutes and allowed to cool.

The support structure (indicated at 600 in FIG. 6A) was then placed ontothe heat treated and wrapped mandrel. Two additional layers of type 1(ASTM D3368) FEP film (provided in Step 12) were then wrapped onto thesupport structure, which was previously placed on the wrapped mandrel.

The wrapped mandrel and the support structure supported thereon werethen heat treated in an air convection oven at about 320° C. for about10 minutes and allowed to cool, forming a polymeric-coated supportstructure.

The polymeric-coated support structure was then trimmed with a scalpelto form a trimmed stent frame, which is generally indicated at 700 andshown illustratively in a flat, plane view in FIG. 6B. Morespecifically, in one manner, the polymeric coating was trimmed about 2mm (0.08″) past the edges of the support structure (600, FIG. 6A) toform a variety of edge profiles 708. In another manner, the polymericcoating was allowed to span entire cells to form a web in each cell. Ineither case, the support structure 600 was fully encapsulated within apolymeric coating 702 to form the trimmed stent frame 700. The trimmedstent frame 700 includes a plurality of leaflet openings 704corresponding in number and generally in shape to the plurality ofleaflet closed cells 606 (FIG. 6A). Further, a slit 706 is formed in thepolymeric coating 702 of each of the small closed cells as shown in FIG.6B. Specifically, each slit 706 is linear and generally parallel to alongitudinal center axis (not shown) of the annular-shaped supportstructure 600.

The trimmed stent frame was then placed onto the combined tool assemblyfrom Step 8. The leaflet portions (102) of the leaflet tools werealigned to the leaflet openings (704 in FIG. 6B) in the trimmed stentframe. The three excess leaflet material areas (315 in FIG. 4) werepulled through the leaflet openings of the stent frame. Each of thethree pairs of straps (312, 314 in FIG. 3A) was pulled through one ofthe slits (706 in FIG. 6B) and wrapped around the trimmed stent frame.Each pair of straps were wrapped in opposing directions relative to eachother. The six straps were then heat tacked to the trimmed stent frameusing a hot soldering iron.

The combined tool assembly (Step 8) and the trimmed stent frame havingthe wrapped and heat tacked straps were then mounted into a rotary chuckmechanism. The rotary chuck mechanism was then adjusted to apply alight, longitudinal compressive load. The excess leaflet material areas(315 in FIG. 4) were then heat tacked to the base tool (500 in FIG. 5)using a hot soldering iron.

The combined tools of Step 18 were then wrapped with an additional 2layers of type 1 (ASTM D3368) FEP film (from Step 12). Three additionallayers of the composite (Step 4) were then overwrapped and tacked downto the trimmed stent frame.

In preparation for a final heat treat, release and sacrificial layers ofa compression tape and compression fiber were applied bothcircumferentially and longitudinally to the assembly from Step 19. Thecompression tape/fiber contact and compress the assembly bothcircumferentially and longitudinally during the subsequent heat treat. Asacrificial layer of compression tape was circumferentially wrapped in ahelical fashion onto the assembly from Step 19. This compression tapehad the properties of the sacrificial compression layer of ePTFEpreviously described in Step 10. An ePTFE compression fiber was thentightly wrapped onto the compression tape. Approximately 100 turns ofthe compression fiber were circumferentially applied in a closely spacedhelical pattern. The ePTFE compression fiber was about 1 mm (0.04″) indiameter and was structured to shrink longitudinally when sufficientlyheated. The clamped assembly was then removed from the rotary chuckmechanism. Three layers of sacrificial compression tape were thenwrapped in a longitudinal fashion around the assembly. Approximately 20wraps of the compression fiber was then longitudinally wrapped over thelongitudinal compression tape.

21). The assembly from Step 20 was then heat treated in an airconvection oven at about 280° C. for about 90 minutes and then roomtemperature water quenched. This heat treatment step facilitates theflow of the thermoplastic fluoroelastomer into the pores of the ePTFEmembrane used to create the leaflet material described in step 4.

The sacrificial compression tapes/fibers were then removed. Thepolymeric materials were trimmed to allow the leaflet and base tools tobe separated. The stent polymeric layers were then trimmed to allowremoval of the stent frame with the attached leaflets. The leaflets werethen trimmed, resulting in a valve assembly as shown in FIG. 8 andgenerally indicated at 800.

The resulting valve assembly 800, according to one embodiment, includesleaflets 802 formed from a composite material with at least onefluoropolymer layer having a plurality of pores and an elastomer presentin substantially all of the pores of the at least one fluoropolymerlayer. Each leaflet 802 is movable between a closed position, shownillustratively in FIG. 9A, in which blood is prevented from flowingthrough the valve assembly, and an open position, shown illustrativelyin FIG. 9B, in which blood is allowed to flow through the valveassembly. Thus, the leaflets 802 of the valve assembly 800 cycle betweenthe closed and open positions generally to regulate blood flow directionin a human patient,

The performance of the valve leaflets in each valve assembly wascharacterized on a real-time pulse duplicator that measured typicalanatomical pressures and flows across the valve, generating an initialor “zero fatigue” set of data for that particular valve assembly. Thevalve assembly was then transferred to a high-rate fatigue tester andwas subjected to approximately 207 million cycles. After each block ofabout 100 million cycles, the valve was then returned to the real-timepulse duplicator and the performance parameters re-measured.

The flow performance was characterized by the following process:

The valve assembly was potted into a silicone annular ring (supportstructure) to allow the valve assembly to be subsequently evaluated in areal-time pulse duplicator. The potting process was performed accordingto the recommendations of the pulse duplicator manufacturer (ViVitroLaboratories Inc., Victoria BC, Canada)

The potted valve assembly was then placed into a real-time left heartflow pulse duplicator system. The flow pulse duplicator system includedthe following components supplied by VSI Vivitro Systems Inc., VictoriaBC, Canada: a Super Pump, Servo Power Amplifier Part Number SPA 3891; aSuper Pump Head, Part Number SPH 5891B, 38.320 cm² cylinder area; avalve station/fixture; a Wave Form Generator, TriPack Part Number TP2001; a Sensor Interface, Part Number VB 2004; a Sensor AmplifierComponent, Part Number AM 9991; and a Square Wave Electro Magnetic FlowMeter, Carolina Medical Electronics Inc., East Bend, N.C., USA.

In general, the flow pulse duplicator system uses a fixed displacement,piston pump to produce a desired fluid flow through the valve undertest.

The heart flow pulse duplicator system was adjusted to produce thedesired flow, mean pressure, and simulated pulse rate. The valve undertest was then cycled for about 5 to 20 minutes.

Pressure and flow data were measured and collected during the testperiod, including ventricular pressures, aortic pressures, flow rates,and pump piston position. FIG. 10 is a graph of data from the heart flowpulse duplicator system.

Parameters used to characterize the valve and to compare to post-fatiguevalues are pressure drop across the open valve during the positivepressure portion of forward flow, effective orifice area, andregurgitant fraction.

Following characterization, the valve assembly was then removed from theflow pulse duplicator system and placed into a high-rate fatigue tester.A Six Position Heart Valve Durability Tester, Part Number M6 wassupplied by Dynatek, Galena, Mo., USA and was driven by a Dynatek DaltaDC 7000 Controller. This high rate fatigue tester displaces fluidthrough a valve assembly with a cycle rate of about 780 cycles perminute. During the test, the valve assembly can be visually examinedusing a tuned strobe light. The pressure drop across the closed valvecan also be monitored as displayed in FIGS. 11A and 11B. Shown in FIGS.11A and 11B is a data set verifying that the high-rate fatigue testerwas producing consistent pressure waveforms.

The valve assembly was continuously cycled and periodically monitoredfor visual and pressure drop changes. After approximately 200 millioncycles, the valve assembly was removed from the high-rate tester andreturned to the real-time pulse duplicator. The pressure and flow datawere collected and compared to the original data collected.

Shown in FIG. 12A is a screen shot displaying measured data output fromthe real-time heart flow pulse duplicator system. Shown are VentricularPressures, Aortic Pressures and Flow Rate. The initial or zero fatiguedata for a particular valve is shown illustratively in FIG. 12A. Thesame measurements were taken and data were collected for the sameparticular valve after 207 million cycles. The 207 million cycle datafor the particular valve is shown illustratively in FIG. 12B. Both setsof measurements were taken at 5 liters per minute flow rate and 70cycles per minute rate. Comparing FIGS. 12A and 12B, it should bereadily appreciated that the waveforms are substantially similar,indicating no substantial change in the valve leaflet performance afterabout 207 million cycles. Pressure drop, effective orifice area (EOA),and regurgitant fraction measured at zero and 207 million cycles aresummarized in Table 1 below.

TABLE 1 Number of cycles Pressure Drop EOA Regurgitant Fraction(Million) (mmHg) (cm²) (%) 0 5.7 2.78 12.7 207 7.7 2.38 9.6

Generally, it was observed that the valve leaflets constructed accordingto the embodiments described herein exhibited no physical or mechanicaldegradation, such as tears, holes, permanent set and the like, after 207million cycles. As a result, there was also no observable change ordegradation in the closed and open configurations of the valve leafletseven after 207 million cycles.

Example 2

An embodiment of a heart valve having polymeric leaflets joined to arigid metallic frame was constructed according to the followingembodiment of a process:

A mandrel 900 was machined from PTFE having a shape shown in FIG. 14.The mandrel 900 has a first end 902 and an opposite second end 904, andextends longitudinally therebetween. The mandrel 900 has an outersurface 910 having three (two shown) generally arcuate, convex lobes912, each generally for forming leaflets (not shown) of a finished valveassembly (not shown). The outer surface 910 also includes a frameseating area 920 for positioning a valve frame (930 in FIG. 15) relativeto the convex lobes 912 prior to formation of leaflets onto the valveframe.

As shown in FIG. 15, a valve frame 930 was laser cut from a length of316 stainless steel tube with an outside diameter of about 25.4 mm and awall thickness of about 0.5 mm in the shape shown in FIG. 15. In theembodiment shown, the valve frame 930 extends axially between a bottomend 932 and an opposite top end defined generally by a plurality ofaxially extending, generally spire shaped posts 934 corresponding to thenumber of leaflets in the intended finished valve assembly (not shown).In the specific embodiment shown, three posts 934 are formed in thevalve frame 930.

Two layers of an about 4 μm thick film of FEP (not shown) was wrappedaround the valve frame 930 and baked in an oven for about 30 minutes atabout 270° C. and allowed to cool. The resulting covered valve frame(for clarity, shown uncovered and indicated at 930) was then slid ontothe mandrel 900 so that the complementary features between the valveframe 930 and mandrel 900 are nested together, as shown in FIG. 16.

A leaflet material was then prepared having a membrane of ePTFE imbibedwith a fluoroelastomer. More specifically, the membrane of ePTFE wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The ePTFE membrane was tested in accordance with themethods described in the Appendix. The ePTFE membrane had a mass perarea of about 0.57 g/m², a porosity of about 90.4%, a thickness of about2.5 μm, a bubble point of about 458 KPa, a matrix tensile strength ofabout 339 MPa in the longitudinal direction and about 257 MPa in thetransverse direction. This membrane was imbibed with the samefluoroelastomer as described in Example 1. The fluoroelastomer wasdissolved in Novec HFE7500, 3M, St Paul, Minn., USA in an about 2.5%concentration. The solution was coated using a mayer bar onto the ePTFEmembrane (while being supported by a polypropylene release film) anddried in a convection oven set to about 145° C. for about 30 seconds.After two coating steps, the resulting composite material ofePTFE/fluoroelastomer had a mass per area of about 3.6 g/m².

The composite material (not shown) was then wound around the assembledmandrel 900 and valve frame 930. In one embodiment, a total of 20 layersof the ePTFE/fluoroelastomer composite was used. Any excess compositematerial that extended beyond the ends of mandrel 900 were twisted andpressed lightly against the ends 902, 904 of the mandrel 900.

The composite material wrapped mandrel was then mounted in a pressurevessel so that a vent port 906 (FIG. 14) in the base or second end 904of the mandrel 900 was plumbed to atmosphere. The vent port 906 extendsfrom the second end 904 axially through the mandrel 900 and communicatesto a generally orthogonally extending vent port 908 that extends throughthe outer surface 910 of the mandrel 900. The vent ports 906, 908, inaddition to other vent ports which may be provided in the mandrel asneeded (not shown), allow trapped air between the composite material andthe mandrel to escape during the molding process.

About 690 KPa (100 psi) of nitrogen pressure was applied to the pressurevessel, forcing the ePTFE/fluoroelastomer composite against the mandrel900 and the valve frame 930. Heat was applied to the pressure vesseluntil the temperature inside the vessel reached about 300° C., about 3hours later. The heater was turned off and the pressure vessel wasallowed to cool to room temperature overnight. This process thermallybonded the layers of ePTFE/fluoroelastomer composite to each other andto the FEP coating on the valve frame 930. The pressure was released andthe mandrel was removed from the pressure vessel.

The ePTFE/fluoroelastomer composite was trimmed circumferentially in twoplaces: first, at the bottom end 932 of the valve frame 930, and second,near the top end of the valve frame 930 along a circle generallyintersecting near the mid-point of each post 934. The resulting valveassembly 940 consisting of the valve frame 930 and the trimmed compositematerial was separated from and slid off the mandrel The molded valveassembly 940, as shown in FIG. 17, includes the valve frame 930 and aplurality of leaflets 950 formed from the trimmed composite material. Inone embodiment, the valve assembly 940 included three leaflets. Inanother embodiment, each leaflet 950 in the valve assembly 940 wasapproximately 40 μm thick.

To help control the degree of opening of the valve, adjacent leafletsabout each post were bonded together. As shown in FIG. 18, the adjacentleaflets 950 a, 950 b were wrapped around the post 934 and bondedtogether to form a seam 954. The seam 954 had a depth 956 extending toat least about 2 mm from the post 934. To support the bond between theadjacent leaflets 950 a, 950 b, an attachment member 952 was fixedlysecured to inner surfaces of the adjacent leaflets 950 a, 950 b therebybridging the seam 954 between the adjacent leaflets 950 a, 950 b. Asshown in FIG. 18, the attachment member 952 was generally rectangular.It should be appreciated, however, that other shapes for the attachmentmember may be utilized. The attachment member 952 was formed from thesame type of composite material used to form the leaflets 950. Theattachment member 952 was fixedly secured to the inner surfaces of theadjacent leaflets 950 a, 950 b using the fluoroelastomer solutionpreviously described. These steps were repeated for the other pairs ofadjacent leaflets of the valve assembly.

The performance and durability of the valve leaflets in this examplewere analyzed in the same manner as described in Example 1. The valveassembly was initially characterized on the same real-time pulseduplicator as described in Example 1 that measured typical anatomicalpressures and flows across the valve, generating an initial or “zerofatigue” set of data for that particular valve assembly. The valve wasthen subjected to accelerated testing as in Example 1. After about 79million cycles, the valve was removed from the high rate fatigue testerand the hydrodynamic performance again characterized as in Example 1.The valve was removed finally at about 198 million cycles. Pressuredrop, EOA and regurgitant fraction measured at about 79 million cyclesand about 198 cycles are summarized in Table 2 below.

FIGS. 13A and 13B display similar results for a similar valve. FIG. 13Ais a graph of measured data output from the heart flow pulse duplicatorsystem taken after about 79 million cycles. The same measurements weretaken for the similar valve after about 198 million cycles, a graph ofwhich is shown illustratively in FIG. 13B. Both sets of measurementswere taken at about 4 liters per minute flow rate and about 70 cyclesper minute rate. Comparing FIGS. 13A and 13B, it should be againappreciated that the waveforms are significantly similar, indicating nosubstantial change in the valve leaflet performance after about 198million cycles. Pressure drop, effective orifice area (EOA), andregurgitant fraction measured at 0, about 79, and about 198 millioncycles are summarized in Table 2 below. These data indicate nosubstantial change in the valve leaflet performance after about 198million cycles.

TABLE 2 Number of Cycles Pressure Drop EOA Regurgitant Fraction(Million) (mmHg) (cm²) (%) 0 6.8 2.56 7.8 79 5.4 2.58 10.25 198 4.4 2.6010.1

Example 3

An embodiment of a heart valve having polymeric leaflets joined to arigid metallic frame was constructed according to the followingembodiment of a process:

A valve support structure or frame 960 was laser cut from a length of316 stainless steel tube with an outside diameter of about 25.4 mm and awall thickness of about 0.5 mm in the shape shown in FIG. 19. In theembodiment shown, the frame 960 extends axially between a bottom end 962and an opposite top end defined generally by a plurality of axiallyextending, generally spire shaped posts 964 corresponding to the numberof leaflets in the intended finished valve assembly (not shown). Aparabolically shaped top edge 968 extends between adjacent posts 964. Inthe specific embodiment shown, three posts 964 and three top edges 968form the top end of the frame 960. The corners of the frame that wouldbe in contact with the leaflet material were rounded using a rotarysander and hand polished. The frame was rinsed with water and thenplasma cleaned using a PT2000P plasma treatment system, Tri-StarTechnologies, El Segundo, Calif., USA.

In one embodiment, a cushion member is provided between at least aportion of the frame and at least a portion of the leaflet to minimizestress related to direct contact between the frame and the leaflet. Acomposite fiber of ePTFE and silicone was created by first imbibing anePTFE membrane with silicone MED-6215 (NuSil, Carpinteria, Calif., USA),slitting it to a width of about 25 mm, and rolling into a substantiallyround fiber. The ePTFE used in this fiber was tested in accordance withthe methods described in the Appendix. The ePTFE membrane had a bubblepoint of about 217 KPa, a thickness of about 10 μm, a mass per area ofabout 5.2 g/m², a porosity of about 78%, a matrix tensile strength inone direction of about 96 MPa, and a matrix tensile strength of about 55MPa in an orthogonal direction. The composite fiber 966 was wrappedaround each of the posts 964 of the frame 960 as shown in FIG. 20.

A mandrel 970 was formed using stereolithography in a shape shown inFIG. 21. The mandrel 970 has a first end 972 and an opposite second end974, and extends longitudinally therebetween. The mandrel 970 has anouter surface 980 having three (two shown) generally arcuate, convexlobes 982, each generally for forming leaflets (not shown) of a finishedvalve assembly (not shown). The outer surface 980 also includes a frameseating area 984 for positioning the frame (960 in FIG. 19) relative tothe convex lobes 982 prior to formation of the valve leaflets onto thevalve frame.

The mandrel 970 was then spray coated with a PTFE mold release agent.Four layers of the ePTFE membrane previously described in this examplewere wrapped around the mandrel. MED-6215 was wiped onto the ePTFE andallowed to wet into and substantially fill the pores of the ePTFE.Excess MED-6215 was blotted off and the frame 960 with the compositefiber 966 wrapped posts 964 was positioned on the mandrel 970 along theframe seating area 984, as shown in FIG. 22. Silicone MED-4720, NuSil,Carpinteria, Calif., USA was placed along the top edges 968 of the frame960 and along the posts 964 of the frame 960 to create a strain reliefwithin the leaflet (not shown). Eight additional layers of ePTFE werewrapped around the frame 960 and mandrel 970. Additional MED-6215 waswiped onto the ePTFE and allowed to wet into and substantially fill thepores of the ePTFE. Another 8 layers of ePTFE were wrapped around theframe 960 and mandrel 970. These layers form a blotter to absorb anyexcess silicone during the molding process and were removed after thesilicone had cured.

Silicone rubber forms (not shown) molded with one surface exactlymatching the inverse shape of the mandrel surface were previouslyfabricated for each of the 3 leaflet-forming features. These forms werespray coated with PTFE mold release and then mated to the matchingfeature of the mandrel. Approximately 50 wraps of an ePTFE fiber (notshown) were wound around the silicone forms to apply generally radialpressure to the valve against the mandrel.

This assembly was then placed in an oven at about 100° C. for about 1hour to cure the silicone. After cooling, the fiber and silicone formswere removed, the 8 layers of blotter ePTFE were peeled away anddiscarded, and the resulting valve (not shown) was slid off of themandrel. The posts were trimmed using wire cutters and the excess lengthof leaflet material and excess length of material at the base of theframe was carefully trimmed using scissors to form a completed valveassembly, which is shown and generally indicated at 990 in FIG. 23.Thus, in one embodiment, the valve assembly 990 was formed having theframe or support structure 960; a plurality of leaflets 992 supported onthe support structure 960 and movable between open and closed positionsto regulate blood flow through the valve assembly 990; and a compositefiber 966 wrapped post 964 located between at least a portion of thesupport structure 960 and at least a portion of each leaflet 992 tominimize stress in the leaflets due to the coupling and/or proximity ofthe leaflets to the support structure. In another embodiment, thecushion member is formed from a composite material with at least onefluoropolymer layer having a plurality of pores and an elastomer presentin substantially all of the pores, as described above.

It should be appreciated that support structures other than asspecifically shown in the figures may be utilized. Further, cushionmembers may be utilized anywhere along the support structure asnecessary to minimize stress in the leaflets due to the coupling and/orproximity of the leaflets to the support structure. For example, cushionmember(s) may be coupled to the support structure along theparabolically shaped top edge.

It should also be appreciated that the cushion members may be formed assheets and wrapped around desired locations along the support structure,or be formed from fibers of various cross sectional shapes and sizes.

It should also be appreciated that the cushion members may be formed astubes and slid over the ends of the support structure, or be slitlongitudinally and positioned around the desired location along thesupport structure.

The leaflets of the complete valve assembly were measured and determinedto have an average thickness at the center of each leaflet of about 120μm.

The valve assembly was then characterized for flow performance andsubjected to accelerated testing as in Example 1. After each block ofabout 50 million cycles, the valve assembly was removed from the highrate fatigue tester and the hydrodynamic performance again characterizedas in Example 1. The valve assembly was removed finally at about 150million cycles and demonstrated acceptable performance and no holeformation.

Comparative Example A

Six valves were constructed in the manner of Example 1 with theexception that the elastomer was not incorporated. The ePTFE materialwas the same as that described in Example 1, but it was not imbibed withthe fluoroelastomer copolymer and was instead coated with adiscontinuous layer of FEP copolymer that served as a thermoplasticadhesive. Valves were constructed as in Example 1 with each leafletcomprising 3 layers of membrane resulting in a final leaflet thicknessaveraging about 20 μm. After hydrodynamic characterization, the valveswere mounted in the Dynatek accelerated tester described in Example 1.By about 40 million cycles, edge delamination and hole formation in theleaflets was observed and the test was stopped.

Comparative Example B

Two valves were constructed in the manner of Example 1 but did notincorporate the elastomer portion of the various embodiments presentedherein. The material employed was thin ePTFE membrane possessingproperties similar to the following: a mass per area of about 2.43 g/m²,a porosity of about 88%, an IBP of about 4.8 KPa, a thickness of about13.8 μm, a matrix tensile strength in one direction of about 662 MPa,and a matrix tensile strength of about 1.2 MPa in the orthogonaldirection. The ePTFE membrane was tested in accordance with the methodsdescribed in the Appendix. Ten layers of the membrane were placed inalternating directions onto a stack and then placed on the tooling asdescribed in Example 1. The tooling was then exposed to about 350° C. ina convection air oven for about 25 minutes, removed and quenched in awater bath. The three pieces of tooling were then inserted into thestent frame and the leaflets bonded to the valve assembly with FEP as inExample 1.

Each valve was subjected to high-rate fatigue testing using thereal-time heart flow pulse duplicator system, as described above. Afterabout 30 million cycles on one valve and about 40 million cycles onanother valve, visual degradation, including stiffening and deformation,was observed and measurable decrease in performance was noted. Inaddition to the visual and measurable degradation in performance, Table3 below summarizes the pressure drop, effective orifice area (EOA), andregurgitant fraction measured after about 40 million cycles.

TABLE 3 Number of Cycles Pressure Drop EOA Regurgitant Fraction(Millions) (mmHg) (cm²) (%) 0 3.9 3.11 8.1 40 × 10⁶ 6.5 2.85 14.1

Example 4

An embodiment of a heart valve having polymeric leaflets comprising acomposite material including a porous polyethylene membrane and anelastomeric material as described above, joined to a metallic valveframe, was constructed according to the following embodiment of aprocess:

A valve frame 1000 was laser machined from a length of seamless MP35Ntubing made in accordance with ASTM F.562 with a full hard temper withan outside diameter of 26 mm and a wall thickness of 0.60 mm. A patterndefining posts 1001 was cut into the tube to form the valve frame 1000,as shown in perspective view in FIG. 24.

The valve frame 1000 was lightly bead blasted to round the edges androughen the surface. The valve frame 1000 was rinsed with water and thensubjected to a plasma cleaning treatment using methods commonly known tothose of ordinary skill in the art.

A composite material was then prepared having a membrane of biaxiallyexpanded ePTFE imbibed with a silicone. More specifically, the membraneof ePTFE was manufactured according to the general teachings describedin U.S. Pat. No. 3,953,566. The ePTFE membrane was tested in accordancewith the methods described previously. The biaxially expanded ePTFEmembrane was amorphously locked, and had the following properties:thickness=0.045 mm, density=0.499 g/cc, matrix tensile strength in thestrongest direction=95.6 MPa, matrix tensile strength in the directionorthogonal to the strongest direction=31.1 MPa, elongation at maximumload in the strongest direction=37%, and elongation at maximum load inthe direction orthogonal to the strongest direction=145%.

This ePTFE membrane was imbibed with silicone 732 Multi-Purpose Sealant(Dow Corning, Midland, Mich.) by first coating the silicone onto a PETfilm using a 0.102 mm drawdown bar. The ePTFE membrane was then laid ontop of the silicone coating and the silicone was allowed to wet into themembrane. A 20 mm wide strip of the composite material was removed fromthe PET film and rolled into a fiber and spirally wrapped around eachpost 1001 on the valve frame 1000 of FIG. 24, as shown in perspectiveview in FIG. 25. This spirally wrapped composite fiber creates a cushionmember 1030 which will be located between a portion of the valve frame1000 and the leaflet 1102 to minimize stress related to direct contactbetween the valve frame 1000 and the leaflet 1102, as shown inperspective view in FIG. 25.

A mandrel 1200 was machined from aluminum in a generally cylindricalshape shown in perspective view in FIG. 26. The mandrel 1200 included afirst end 1202 and an opposing second end 1203.

The mandrel had twelve 0.5 mm diameter holes 1207 that pass from theouter surface 1204 to a central cavity 1206 running within the center ofthe mandrel. Twelve holes 1207 were positioned in two rows distributedcircumferentially around the mandrel, one row hidden from view by thevalve frame in FIG. 26. These holes 1207, in communication with thecentral cavity 1206, allowed trapped air to be vented away from thevalve assembly during molding.

Two layers of a sacrificial composite material comprising ePTFE andpolyimide with a thickness of approximately 0.004 mm were wrapped aroundmandrel 1200.

A composite material was then prepared having a microporous polyethylenemembrane imbibed with a silicone. The microporous polyethylene membranewas obtained from a Pall Corp. (Port Washington, N.Y.) PE Kleen 5 nmwater filter cartridge ABD1UG53EJ, which contains a hydrophobic highdensity polyethylene (HDPE) membrane. The microporous polyethylenemembrane was tested in accordance with the methods described previouslyand had the following properties: thickness=0.010 mm, density=0.642g/cc, matrix tensile strength in the strongest direction=214 MPa, matrixtensile strength in the direction orthogonal to the strongestdirection=174 MPa, elongation at maximum load in the strongestdirection=62%, elongation at maximum load in the direction orthogonal tothe strongest direction=157%, a fiber diameter of less than about 1 μm,a mean flow pore size of 0.0919 μm, and a specific surface area of 28.7m²/cc. It is anticipated that microporous polyethylene membrane may havea mean flow pore sizes of less than about 5 μm, less than about 1 μm,and less than about 0.10 μm, in accordance with embodiments.

The microporous polyethylene membrane was soaked in acetone forapproximately 72 hours and allowed to air dry at room temperature. Acoating of 732 Multipurpose Sealant was applied to a PET film using a0.51 mm drawdown bar. The microporous polyethylene membrane was thenlaid on top of the silicone coating and the silicone was allowed to wetinto the membrane. The silicone and polyethylene composite material wasremoved from the PET and wrapped around the mandrel 1200 and thesacrificial PTFE/Polyamide composite material, for a total of twolayers.

The valve frame 1000 with posts 1001 covered by the cushion member 1030was slid onto the mandrel 1200, on top of the two layers. Holes werepoked through the previously applied layers above the vent holes and thevalve frame 1000 was positioned so a base 1003 of the valve frame 1000covered one row of the vent holes 1207 (hidden) as shown in FIG. 26.

Five more layers of the silicone/polyethylene composite material werewrapped around the valve frame 1000.

Eight layers of the ePTFE membrane previously described in this examplewere wrapped on top of the previous layers to create a sacrificialblotter layer to absorb any excess silicone. Two layers of a sacrificialcomposite material comprising ePTFE and polyimide with a thickness ofapproximately 0.004 mm were wrapped around the mandrel and previouslyapplied components. Adhesive-backed polyimide tape was used to attachthe ePTFE/polyimide composite to the mandrel at each end and to seal thelongitudinal seam.

The mandrel 1200 with previously applied components was then mounted ina pressure vessel so that a vent port 1211 in communication with thecentral cavity 1206 in the first end 1202 of the mandrel 1200 wasplumbed to atmosphere. The central cavity 1206 extends from the firstend 1202 axially through the mandrel 1200 and in communication with the12 previously described vent holes 1207.

About 414 KPa (60 psi) of helium pressure was applied to the pressurevessel, forcing the microporous polyethylene and silicone compositematerial against the mandrel 1200 and the valve frame 1000. Heat wasapplied to the pressure vessel until the temperature inside the mandrelreached about 95° C., about 28 minutes later. The heat was removed andthe pressure vessel was allowed to cool to room temperature. Thisprocess bonded the layers of the silicone/polyethylene compositematerial to each other and to the valve frame 1000. The pressure wasreleased and the mandrel 1200 was removed from the pressure vessel. Thevalve assembly 1010 was slid off of the mandrel 1200 and the outer layerof the sacrificial ePTFE/polyimide composite material was removed, asshown in perspective view in FIG. 27.

A shaped mandrel 1300 was machined from aluminum in a generallycylindrical shape shown in perspective view in FIG. 28. The mandrel 1300includes a first end 1302, an opposing second end 1303, and a centralportion 1305 therebetween defining concave features 1309.

The mandrel 1300 had three 0.5 mm diameter holes 1307 that pass from theouter surface 1304 to a central cavity 1306 running within the center ofthe mandrel 1300. The holes 1307 are located at the end of the concavefeature closest to the shaped mandrel first end 1302, and are incommunication with the central cavity 1306. These holes 1307 allowedtrapped air to be vented away from the valve assembly 1010 duringmolding.

The valve assembly 1010 was slid onto the shaped mandrel 1300 and thevalve frame 1000 was aligned with the concave features 1309 of themandrel 1300 as shown in FIG. 28. The composite material with thesacrificial layers were pressed against the mandrel 1300 and taped toeither ends of the mandrel 1300 using adhesive-backed polyimide tape. Atube of sacrificial composite material comprising ePTFE and polyimidewas prepared by wrapping a sheet of the composite material around a 23.9mm mandrel and taping the axial seam with adhesive-backed polyimidetape. This tube was slid over the valve assembly 1010 while mounted onthe shaped mandrel and taped to the ends of the shaped mandrel usingadhesive-backed polyimide tape.

The shaped mandrel 1300 with previously applied components was thenmounted in a pressure vessel so that a vent port 1311, in communicationwith the central cavity 1306, in the first end 1302 of the mandrel 1300was plumbed to atmosphere. The central cavity 1306 extends from thefirst end 1302 axially through the mandrel 1300 and communicates to thepreviously described vent holes 1307.

About 689 KPa (100 psi) of helium pressure was applied to the pressurevessel, forcing the microporous polyethylene and silicone compositematerial against the mandrel 1300 and the valve frame 1000. Heat wasapplied to the pressure vessel until the temperature inside the mandrelreached about 98° C., about 13 minutes later. The heat was removed andthe pressure vessel was allowed to cool to room temperature. Thisprocess forced the layers of the silicone/polyethylene compositematerial to take the shape of the shaped mandrel 1300 with leafletportions 1109 being drawn into and taking the shape of a portion of theconcave features 1309. The valve assembly 1010 was slid off the mandrel1300 and the sacrificial ePTFE/polyimide composite material and thesacrificial ePTFE blotter material was removed.

The microporous polyethylene and silicone composite was trimmed so thatapproximately 2 mm of the composite extended beyond the base of theframe and beyond the tips of the frame posts as shown in FIG. 29.

The thickness of the leaflets 1102 was approximately 139 μm and thepercent weight of the silicone within the composite material was about69%.

The performance of the valve leaflets in this valve assembly werecharacterized on a real-time pulse duplicator that measured typicalanatomical pressures and flows across the valve, generating an initialor “zero fatigue” set of data for that particular valve assembly. Theflow performance was characterized by the following process:

The valve assembly was pressed into a silicone annular ring (supportstructure) to allow the valve assembly to be subsequently evaluated in areal-time pulse duplicator.

The potted valve assembly was then placed into a real-time left heartflow pulse duplicator system. The flow pulse duplicator system includedthe following components supplied by VSI Vivitro Systems Inc., VictoriaBC, Canada: a Super Pump, Servo Power Amplifier Part Number SPA 3891; aSuper Pump Head, Part Number SPH 5891B, 38.320 cm² cylinder area; avalve station/fixture; a Wave Form Generator, TriPack Part Number TP2001; a Sensor Interface, Part Number VB 2004; a Sensor AmplifierComponent, Part Number AM 9991; and a Square Wave Electro Magnetic FlowMeter, Carolina Medical Electronics Inc., East Bend, N.C., USA.

In general, the flow pulse duplicator system uses a fixed displacement,piston pump to produce a desired fluid flow through the valve undertest.

The heart flow pulse duplicator system was adjusted to produce thedesired flow, mean pressure, and simulated pulse rate. The valve undertest was then cycled for about 5 to 20 minutes.

Pressure and flow data were measured and collected during the testperiod, including ventricular pressures, aortic pressures, flow rates,and pump piston position.

The valve in this example had a pressure drop of 11.3 mm Hg, EOA of 2.27cm² and regurgitant fraction of 15.4%

Example 5

Another embodiment of a heart valve having polymeric leaflets comprisinga composite material including a microporous polyethylene membrane andan elastomeric material as described above, joined to a metallic valveframe, was constructed according to the following embodiment of aprocess:

A valve frame 1000 was prepared as in Example 4.

A composite material was prepared having a membrane of microporouspolyethylene imbibed with a silicone. The microporous polyethylenemembrane was obtained from a Pall Corp. (Port Washington, N.Y.) PE Kleen5 nm water filter cartridge ABD1UG53EJ, which contains a hydrophobichigh density polyethylene (HDPE) membrane. The microporous polyethylenemembrane was stretched on a biaxial expansion machine. The microporouspolyethylene membrane was mounted on the pins of the expansion machinewith the pins positioned 70 mm apart in a first direction and 150 mmapart in the direction orthogonal to the first direction. Themicroporous polyethylene membrane was allowed to dwell for 60 seconds ina heated chamber within the biaxial expansion machine, reaching a webtemperature of 129° C. The pins were then translated in the firstdirection from 70 mm to 84 mm at a rate of 0.7%/second while the pins inthe direction orthogonal to the first direction were translated from 150mm to 420 mm at a rate of 10%/second. The membrane was removed from theheated chamber while restrained by the pins and allowed to air cool toroom temperature.

The stretched microporous polyethylene membrane was tested in accordancewith the methods described previously and had the following properties:thickness=0.006 mm, density=0.524 g/cc, matrix tensile strength in thefirst direction=156 MPa, matrix tensile strength in the directionorthogonal to the first direction=474 MPa, elongation at maximum load inthe first direction=167%, elongation at maximum load in the directionorthogonal to the first direction=19%, a fiber diameter of less thanabout 1 μm, a mean flow pore size of 0.1011 μm, and a specific surfacearea of 18.3 m²/cc. It is anticipated that microporous polyethylenemembrane may have a mean flow pore size of less than about 5 μm, lessthan about 1 μm, and less than about 0.10 μm, in accordance withembodiments.

The stretched microporous polyethylene membrane was imbibed withsilicone 734 Flowable Sealant (Dow Corning, Midland, Mich.) by firstcoating the silicone onto a PET film using a 0.25 mm drawdown bar. Thepolyethylene membrane was then laid on top of the silicone coating andthe silicone was allowed to wet into the membrane. A 20 mm wide strip ofthe composite material was removed from the PET film and rolled/twistedinto a fiber and spirally wrapped around each post 1001 on the valveframe 1000 of FIG. 25. This spirally wrapped composite fiber creates acushion member 1030 which will be located between a portion of the valveframe 1000 and the leaflet 1102 to minimize stress related to directcontact between the valve frame 1000 and the leaflet 1102, as shown inFIG. 29.

A mandrel 1200 as described in Example 1 and shown in FIG. 26 wasobtained. Two layers of a sacrificial composite material comprisingePTFE and polyimide with a thickness of approximately 0.004 mm werewrapped around mandrel 1200.

A composite material of stretched microporous polyethylene membrane andsilicone was prepared as described previously in this example.

The silicone and microporous polyethylene membrane composite materialwas circumferentially wrapped around the mandrel 1200 and thesacrificial PTFE/Polyamide composite material, for a total of twolayers. The first direction of the stretched microporous polyethylenemembrane was aligned with the long axis of the mandrel 1300 while it waswrapped.

The valve frame 1000 with fiber covered posts 1001 was slid onto themandrel 1200, on top of the two layers. Holes were poked through thepreviously applied layers above the vent holes and the valve frame waspositioned so a base 1003 of the valve frame 1000 covered one row of thevent holes 1207 (hidden) as shown in FIG. 26.

A small amount of silicone was applied by hand to the frame to provideadditional adhesive between the frame and the circumferentially wrappedcomposite material.

Four more layers of the silicone and microporous polyethylene membranecomposite material were wrapped around the valve frame 1000.

Eight layers of the ePTFE membrane previously described in Example 4were wrapped on top of the previous layers to create a sacrificialblotter layer to absorb any excess silicone. Two layers of a sacrificialcomposite material comprising ePTFE and polyimide with a thickness ofapproximately 0.004 mm were wrapped around the mandrel and previouslyapplied components. Adhesive-backed polyimide tape was used to attachthe ePTFE/polyimide composite to the mandrel at each end and to seal thelongitudinal seam.

The mandrel 1200 with previously applied components was then mounted ina pressure vessel so that a vent port 1211, in communication with thecentral cavity 1206, in the first end 1202 of the mandrel 1200 wasplumbed to atmosphere. The central cavity 1206 extends from the firstend 1202 axially through the mandrel 1200 and communicates to the 12previously described vent holes 1207.

About 414 KPa (60 psi) of helium pressure was applied to the pressurevessel, forcing the microporous polyethylene membrane and siliconecomposite material against the mandrel 1200 and the valve frame 1000.Heat was applied to the pressure vessel until the temperature inside themandrel reached about 66° C., about 20 minutes later. The heat wasremoved and the pressure vessel was allowed to cool to room temperature.This process bonded the layers of the silicone/polyethylene compositematerial to each other and to the valve frame 1000. The pressure wasreleased and the mandrel 1200 was removed from the pressure vessel. Thevalve assembly 1010 was slid off of the mandrel 1200 and the outer layerof the sacrificial ePTFE/polyimide composite material was removed, asshown in perspective view in FIG. 26.

A shaped mandrel 1300 as described in Example 4 was obtained as shown inFIG. 28. The valve assembly 1010 was slid onto the shaped mandrel 1300and the valve frame 1000 was aligned with the concave features 1309 ofthe mandrel 1300 as shown in FIG. 28. The silicone and microporouspolyethylene membrane composite material with the sacrificial layerswere pressed against the mandrel 1300 and taped to either ends of themandrel 1300 using adhesive-backed polyimide tape. A tube of sacrificialcomposite material comprising ePTFE and polyimide was prepared bywrapping a sheet of the composite material around a 23.9 mm mandrel andtaping the axial seam with adhesive-backed polyimide tape. This tube wasslid over the valve assembly 1010 while mounted on the shaped mandreland taped to the ends of the shaped mandrel using adhesive-backedpolyimide tape.

The shaped mandrel 1300 with previously applied components was thenmounted in a pressure vessel so that a vent port 1311 in the first end1302 of the mandrel 1300 was plumbed to atmosphere.

About 551 KPa (80 psi) of air pressure was applied to the pressurevessel, forcing the microporous polyethylene and silicone compositematerial against the mandrel 1300 and the valve frame 1000. Heat wasapplied to the pressure vessel until the temperature inside the mandrelreached about 95° C., about 13 minutes later. The heat was removed andthe pressure vessel was allowed to cool to room temperature. Thisprocess forced the layers of the silicone and microporous polyethylenemembrane composite material to take the shape of the shaped mandrel 1300with leaflet portions 1109 being drawn into and taking the shape of aportion of the concave features 1309. The valve assembly 1010 was slidoff the mandrel 1300 and the sacrificial ePTFE/polyimide compositematerial and the sacrificial ePTFE blotter material was removed.

The polyethylene/silicone composite was trimmed so that approximately 2mm of the composite extended beyond the base of the frame and beyond thetips of the frame posts as shown in FIG. 29.

The thickness of the leaflets 1102 was approximately 53 μm and thepercent weight of the silicone within the composite material was about65%.

The performance of the valve leaflets in this valve assembly werecharacterized on a real-time pulse duplicator that measured typicalanatomical pressures and flows across the valve, generating an initialor “zero fatigue” set of data for that particular valve assembly. Theflow performance was characterized by the process as described inExample 4.

The valve in this example had a pressure drop of 8.7 mm Hg, EOA of 2.49cm² and regurgitant fraction of 16.7%.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the present inventionwithout departing from the spirit or scope of the invention. Thus, it isintended that the present invention cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

APPENDIX

As used in this disclosure, matrix tensile strength refers to thetensile strength of a porous fluoropolymer specimen under specifiedconditions. The porosity of the specimen is accounted for by multiplyingthe tensile strength by the ratio of density of the polymer to thedensity of the specimen.

The term membrane as used herein refers to a porous sheet of materialcomprising a single composition, such as, but not limited to, expandedfluoropolymer.

The term composite material as used herein refers to a combination of amembrane, such as, but not limited to, expanded fluoropolymer, and anelastomer, such as, but not limited to, a fluoroelastomer. The elastomermay be imbibed within a porous structure of the membrane, coated on oneor both sides of the membrane, or a combination of coated on and imbibedwithin the membrane.

The term laminate as used herein refers to multiple layers of membrane,composite material, or other materials, such as elastomer, andcombinations thereof.

The term imbibe used herein refers to any process used to at leastpartially fill pores with a secondary material.

For porous membrane having pores substantially filled with elastomer,the elastomer can be dissolved or degraded and rinsed away using anappropriate solvent in order to measure desired properties.

As the term “elastomer” is used herein it defines a polymer or a mixtureof polymers that has the ability to be stretched to at least 1.3 timesits original length and to retract rapidly to approximately its originallength when released. The term “elastomeric” is intended to describe aproperty whereby a polymer displays stretch and recovery propertiessimilar to an elastomer, although not necessarily to the same degree ofstretch and/or recovery.

As the term “thermoplastic” is used herein it defines a polymer that ismelt processable. In contrast to a thermoplastic polymer, a “thermoset”polymer is hereby defined as a polymer that solidifies or “sets”irreversibly when cured.

As used herein, the terms “fibril” and “fiber” are used interchangeably.As used herein, the terms “pores” and “interstices” are usedinterchangeably.

As used herein, the term synthetic polymer refers to polymer not derivedfrom biological tissue.

The term leaflet as used herein in the context of prosthetic valvesrefers to a component of a one-way valve wherein the leaflet is operableto move between an open and closed position under the influence of apressure differential. In an open position, the leaflet allows blood toflow through the valve. In a closed portion, the leaflet substantiallyblocks retrograde flow through the valve. In embodiments comprisingmultiple leaflets, each leaflet cooperates with at least one neighboringleaflet to block the retrograde flow of blood. Leaflets in accordancewith embodiments provided herein comprise one or more layers of acomposite.

Testing Methods

It should be understood that although certain methods and equipment aredescribed below, any method or equipment determined suitable by one ofordinary skill in the art may be alternatively utilized.

Effective Orifice Area

One measure of the quality of a valve is the effective orifice area(EOA), which can be calculated as follows:EOA(cm²)=Q_(rms)/(51.6*(ΔP)^(1/2)) where Q_(rms) is the root mean squaresystolic/diastolic flow rate (cm³/s) and ΔP is the meansystolic/diastolic pressure drop (mmHg).

Surface Area Per Unit Mass

As used in this application, the surface area per unit mass, expressedin units of m²/g, was measured using the Brunauer-Emmett-Teller (BET)method on a Coulter SA3100Gas Adsorption Analyzer, Beckman Coulter Inc.Fullerton Calif., USA. To perform the measurement, a sample was cut fromthe center of the expanded fluoropolymer membrane and placed into asmall sample tube. The mass of the sample was approximately 0.1 to 0.2g. The tube was placed into the Coulter SA-Prep Surface Area Outgasser(Model SA-Prep, P/n 5102014) from Beckman Coulter, Fullerton Calif., USAand purged at about 110° C. for about two hours with helium. The sampletube was then removed from the SA-Prep Outgasser and weighed. The sampletube was then placed into the SA3100 Gas adsorption Analyzer and the BETsurface area analysis was run in accordance with the instrumentinstructions using helium to calculate the free space and nitrogen asthe adsorbate gas.

Bubble Point and Mean Flow Pore Size

Bubble point and mean flow pore size were measured according to thegeneral teachings of ASTM F31 6-03 using a capillary flow Porometer,Model CFP 1500AEXL from Porous Materials, Inc., Ithaca N.Y., USA. Thesample membrane was placed into the sample chamber and wet with SilWickSilicone Fluid (available from Porous Materials Inc.) having a surfacetension of about 20.1 dynes/cm. The bottom clamp of the sample chamberhad an about 2.54 cm diameter hole. Isopropyl alcohol was used as thetest fluid. Using the Capwin software version 7.73.012 the followingparameters were set as specified in the table below. As used herein,mean flow pore size and pore size are used interchangeably.

Parameter Set Point Maxflow (cm³/m) 200000 Bublflow (cm³/m) 100 F/PT(old bubltime) 50 Minbpress (PSI) 0 Zerotime (sec) 1 V2incr (cts) 10Preginc (cts) 1 Pulse delay (sec) 2 Maxpre (PSI) 500 Pulse width (sec)0.2 Mineqtime (sec) 30 Presslew (cts) 10 Flowslew (cts) 50 Eqiter 3Aveiter 20 Maxpdif (PSI) 0.1 Maxfdif (PSI) 50 Sartp (PSI) 1 Sartf(cm³/m) 500Presence of Elastomer within the Pores

The presence of elastomer within the pores can be determined by severalmethods known to those having ordinary skill in the art, such as surfaceand/or cross section visual, or other analyses. These analyses can beperformed prior to and after the removal of elastomer from the leaflet.

Diameter of Fibrils and Fibers

The average diameter of the fibrils and fibers was estimated byexamining scanning electron micrographs that were obtained having at amagnification suitable for showing numerous fibrils or fibers, such asthe scanning electron microscopy (SEM) micrographs of FIGS. 7A-C, 30 and31. In the case of a composite material, it may be necessary to extractthe elastomer or other material that may be filling the pores, by anysuitable means, to expose the fibrils or fibers.

Mass, Thickness, and Density of ePTFE Membranes

Membrane thickness was measured by placing the membrane between the twoplates of a Käfer FZ1000/30 thickness snap gauge Käfer MessuhrenfabrikGmbH, Villingen-Schwenningen, Germany. The average of the threemeasurements was reported.

Membrane samples were die cut to form rectangular sections about 2.54 cmby about 15.24 cm to measure the weight (using a Mettler-Toledoanalytical balance model AG204) and thickness (using a Käfer Fz1000/30snap gauge). Using these data, density was calculated with the followingformula: ρ=m/(w*l*t), in which: ρ=density (g/cm³), m=mass (g), w=width(cm), l=length (cm), and t=thickness (cm). The average of threemeasurements was reported.

Matrix Tensile Strength (MTS) of ePTFE Membranes

Tensile break load was measured using an INSTRON 122 tensile testmachine equipped with flat-faced grips and a 0.445 kN load cell. Thegauge length was about 5.08 cm and the cross-head speed was about 50.8cm/min. The sample dimensions were about 2.54 cm by about 15.24 cm. Forhighest strength measurements, the longer dimension of the sample wasoriented in the highest strength direction. For the orthogonal MTSmeasurements, the larger dimension of the sample was orientedperpendicular to the highest strength direction. Each sample was weighedusing a Mettler Toledo Scale Model AG204, then the thickness wasmeasured using the Käfer FZ1000/30 snap gauge; alternatively, anysuitable means for measuring thickness may be used. The samples werethen tested individually on the tensile tester. Three different sectionsof each sample were measured. The average of the three maximum loads(i.e., peak force) measurements was reported. The longitudinal andtransverse matrix tensile strengths (MTS) were calculated using thefollowing equation: MTS=(maximum load/cross-section area)*(bulk densityof PTFE)/(density of the porous membrane), where the bulk density of thePTFE was taken to be about 2.2 g/cm³.

Mass, Thickness, and Density of Polyethylene Membranes

Membrane samples were die cut to form circular sections about 5.0 cm indiameter to measure the weight (using a Sartorius analytical balancemodel MC210P) and thickness (using a Starrett 3732×FL-1 micrometer).Using these data, density was calculated with the following formula:ρ=m/(w*l*t), in which: ρ=density (g/cm³), m=mass (g), w=width (cm),l=length (cm), and t=thickness (cm). The average of three measurementswas reported.

Matrix Tensile Strength (MTS) of Polyethylene Membranes

Tensile break load was measured using an INSTRON 5500R tensile testmachine equipped with flat-faced grips and a 0.890 kN load cell. Thegauge length was about 2.54 cm and the strain rate was approximately1000%/min. The sample dimensions were about 0.47 cm by about 3.90 cm.For highest strength measurements, the longer dimension of the samplewas oriented in the highest strength direction. For the orthogonal MTSmeasurements, the larger dimension of the sample was orientedperpendicular to the highest strength direction. The thickness of eachsample was measured using a Starrett 3732×FL-1 micrometer;alternatively, any suitable means for measuring thickness may be used.The samples were then tested individually on the tensile tester. Fivedifferent sections of each sample were measured. The average of the Fivemaximum loads (i.e., peak force) measurements was reported. Thelongitudinal and transverse matrix tensile strengths (MTS) werecalculated using the following equation: MTS=(maximum load/cross-sectionarea)*(bulk density of polyethylene)/(density of the porous membrane),where the bulk density of the polyethylene was taken to be about 0.94g/cm³.

Flexural stiffness was measured by following the general procedures setforth in ASTM D790. Unless large test specimens are available, the testspecimen must be scaled down. The test conditions were as follows. Theleaflet specimens were measured on a three-point bending test apparatusemploying sharp posts placed horizontally about 5.08 mm from oneanother. An about 1.34 mm diameter steel bar weighing about 80 mg wasused to cause deflection in the y (downward) direction, and thespecimens were not restrained in the x direction. The steel bar wasslowly placed on the center point of the membrane specimen. Afterwaiting about 5 minutes, the y deflection was measured. Deflection ofelastic beams supported as above can be represented by: d=F*L³/48*El,where F (in Newtons) is the load applied at the center of the beamlength, L (meters), so L=½ distance between suspending posts, and El isthe bending stiffness (Nm). From this relationship the value of El canbe calculated. For a rectangular cross-section: l=t³*w/12, wherel=cross-sectional moment of inertia, t=specimen thickness (meters),w=specimen width (meters). With this relationship, the average modulusof elasticity over the measured range of bending deflection can becalculated.

Surface Area Measurements

The surface area per unit mass (specific surface area), expressed inunits of m²/g, of the microporous polymer membrane was measured usingthe Brunauer-Emmett-Teller (BET) method on a Coulter SA3100 GasAdsorption Analyzer (Beckman Coulter Inc., Fullerton, Calif.). A samplewas cut from the center of the microporous polymer membrane sheet andplaced into a small sample tube. The mass of the sample wasapproximately 0.1 to 0.2 grams. The tube was placed into the CoulterSA-Prep Surface Area Outgasser, (Model SA-PREP, P/N 5102014) fromBeckman Coulter Inc., Fullerton, Calif. and purged at 110 C for 2 hourswith helium. The sample tube was then removed from the SA-Prep Outgasserand weighed. The sample tube was then placed into the SA3100 GasAdsorption Analyzer and the BET surface area analysis was run inaccordance with the instrument instructions using helium to calculatethe free space and nitrogen as the adsorbate gas. A single measurementwas recorded for each sample.

It is useful to convert the specific surface area as expressed in unitsof m²/g to specific surface area expressed in units of m²/cc in order tocompare the specific surface areas of materials of different densities.To do so, multiply the specific surface area expressed in m²/g by thedensity of the sample material expressed in g/cc. The density of PTFEwas taken to be 2.2 g/cc and the density of polyethylene was taken to be0.98 g/cc.

What is claimed is:
 1. A valve, comprising: a support structure, and atleast one leaflet being supported on the support structure and movablebetween open and closed positions, each leaflet including a compositematerial comprising at least one synthetic polymer membrane and anelastomer, the at least one synthetic polymer membrane comprising fibersthat define space therebetween, wherein a diameter of a majority of thefibers is less than about 1 μm, the space between the fibers definingpores, the elastomer being disposed in substantially all of the pores.2. The valve of claim 1, wherein the composite material further includesa layer of an elastomer.
 3. The valve of claim 1, wherein the at leastone synthetic polymer membrane is fluoropolymer membrane.
 4. The valveof claim 1, wherein the at least one synthetic polymer membrane isporous polyethylene membrane.
 5. The valve of claim 1, wherein theelastomer is silicone.
 6. The valve of claim 1, wherein the elastomer isa fluoroelastomer.
 7. The valve of claim 1, wherein the elastomer is aurethane.
 8. The valve of claim 1, wherein the elastomer is a TFE/PMVEcopolymer.
 9. The valve of claim 8, wherein the TFE/PMVE copolymercomprises essentially of between about 40 and 80 weight percentperfluoromethyl vinyl ether and complementally 60 and 20 weight percenttetrafluoroethylene.
 10. The valve of claim 4, wherein the porouspolyethylene membrane has a matrix tensile strength in at least onedirection greater than about 150 MPa.
 11. The valve of claim 1, whereinthe leaflet has a thickness of less than about 350 μm.
 12. The valve ofclaim 1, wherein the composite material comprises at least one layer ofthe synthetic polymer membrane.
 13. The valve of claim 1, wherein thecomposite material comprises more than two layers of the syntheticpolymer membrane.
 14. The valve of claim 13, wherein the leafletcomprises overlapping wrappings of the composite material, wherein thelayers of the synthetic polymer membrane are defined by a number ofoverlapping wrappings of the composite material.
 15. The valve of claim14, wherein the leaflet has a ratio of leaflet thickness (μm) to numberof layers of synthetic polymer membrane of less than about
 20. 16. Thevalve of claim 1, wherein the support structure is selectivelydiametrically adjustable for endovascular delivery and deployment at atreatment site, wherein the valve is operable to be a prosthetic heartvalve.
 17. The valve of claim 1, wherein the pores have a pore size thatis less than about 5 μm.
 18. The valve of claim 1, wherein the poreshave a pore size that is less than about 1 μm.
 19. The valve of claim 1,wherein the pores have a pore size that is less than about 0.1 μm. 20.The valve of claim 1, wherein the diameter of a majority of the fibersis less than about 0.1 μm.
 21. The valve of claim 1, wherein the atleast one synthetic polymer membrane comprises substantially only offibers.
 22. The valve of claim 1, wherein the composite materialcomprises elastomer by weight in a range from about 10% to about 90%.23. The valve of claim 14, wherein the leaflet has a ratio of leafletthickness (μm) to number of layers of synthetic polymer membrane of lessthan about
 20. 24. The valve of claim 14, wherein the leaflet has atleast 10 layers and the composite material comprising less than about50% synthetic polyethylene membrane by weight.
 25. The valve of claim 1,further comprising: a cushion member located between at least a portionof the support structure and at least a portion of the leaflet, whereinthe cushion member comprises a second composite material with at leastone synthetic polymer membrane having a plurality of pores and anelastomer present in substantially all of the pores.
 26. The valve ofclaim 25, wherein the cushion member includes porous polyethylenemembrane.
 27. The valve of claim 25, wherein the cushion member at leastpartially covers the at least a portion of the support structure toprovide a cushion between the at least a portion of the supportstructure and the leaflet.
 28. The valve of claim 25, wherein thecushion member is wrapped about the at least a portion of the supportstructure to provide a cushion between the at least a portion of thesupport structure and the leaflet.
 29. The valve of claim 25, whereinthe support structure includes a first end and a second end opposite thefirst end, the second end comprising a plurality of posts extendinglongitudinally therefrom, wherein the cushion member is wrapped abouteach post to provide a cushion between the post and a portion of theleaflet coupled to at least a portion of the post.
 30. The valve ofclaim 1, wherein the composite material comprises at least one layer ofthe synthetic polymer membrane, wherein the at least one syntheticpolymer membrane is expanded fluoropolymer membrane, wherein theelastomer is a TFE/PMVE copolymer, and wherein the valve is operable tobe a prosthetic heart valve.
 31. The valve of claim 1, wherein thecomposite material comprises at least one layer of the synthetic polymermembrane, wherein the at least one synthetic polymer membrane is porouspolyethylene membrane, wherein the elastomer is a silicone, and whereinthe valve is operable to be a prosthetic heart valve.
 32. A valve,comprising: a support structure, and at least one leaflet beingsupported on the support structure and movable between open and closedpositions, each leaflet including a composite material comprising atleast one synthetic polymer membrane having a plurality of pores and anelastomer present in substantially all of the pores, the compositematerial comprising elastomer by weight in a range from about 10% toabout 90%.
 33. The valve of claim 32, wherein the composite materialcomprises less than about 70% synthetic polymer membrane by weight. 34.The valve of claim 32, wherein the composite material comprises lessthan about 60% synthetic polymer membrane by weight.
 35. The valve ofclaim 32, wherein the composite material comprises less than about 50%synthetic polymer membrane by weight.
 36. The valve of claim 32, whereinthe composite material further includes a layer of an elastomer.
 37. Thevalve of claim 32, wherein the at least one synthetic polymer membraneis fluoropolymer membrane.
 38. The valve of claim 32, wherein thesynthetic polymer membrane is porous polyethylene membrane.
 39. Thevalve of claim 38, wherein the pores are defined by a fibrous structurecomprising fibers that have an average fiber diameter of less than about1 μm.
 40. The valve of claim 38, wherein the pores are defined by afibrous structure comprising fibers that have an average fiber diameterof less than about 0.1 μm.
 41. The valve of claim 38, wherein theelastomer is silicone.
 42. The valve of claim 32, wherein the elastomeris a fluoroelastomer.
 43. The valve of claim 32, wherein the elastomeris a urethane.
 44. The valve of claim 42, wherein the elastomer is aTFE/PMVE copolymer.
 45. The valve of claim 44, wherein the TFE/PMVEcopolymer consists essentially of between about 40 and 80 weight percentperfluoromethyl vinyl ether and complementally 60 and 20 weight percenttetrafluoroethylene.
 46. The valve of claim 38, wherein the porouspolyethylene membrane has a matrix tensile strength in at least onedirection greater than about 150 MPa.
 47. The valve of claim 32, whereinthe leaflet has a thickness of less than about 350 μm.
 48. The valve ofclaim 32, wherein the composite material comprises at least one layer ofthe synthetic polymer membrane.
 49. The valve of claim 32, wherein thecomposite material comprises more than two layers of the syntheticpolymer membrane.
 50. The valve of claim 49, wherein the leafletcomprises overlapping wrappings of the composite material, wherein thelayers of the synthetic polymer membrane are defined by a number ofoverlapping wrappings of the composite material.
 51. The valve of claim48, wherein the leaflet has a ratio of leaflet thickness (μm) to numberof layers of synthetic polymer membrane of less than about
 20. 52. Thevalve of claim 38, wherein the leaflet has at least 10 layers of porouspolyethylene membrane and the composite material comprising less thanabout 50% synthetic polyethylene membrane by weight.
 53. The valve ofclaim 32, wherein the pores have a pore size that is less than about 5μm.
 54. The valve of claim 32, wherein the pores have a pore size thatis less than about 1 μm.
 55. The valve of claim 32, wherein the poreshave a pore size that is less than about 0.10 μm.
 56. The valve of claim32, further comprising: a cushion member located between at least aportion of the support structure and at least a portion of the leaflet,wherein the cushion member comprises a second composite material with atleast one synthetic polymer membrane having a plurality of pores and anelastomer present in substantially all of the pores.
 57. The valve ofclaim 56, wherein the cushion member includes porous polyethylenemembrane.
 58. The valve of claim 56, wherein the cushion member at leastpartially covers the at least a portion of the support structure toprovide a cushion between the at least a portion of the supportstructure and the leaflet.
 59. The valve of claim 57, wherein thecushion member is wrapped generally helically about the at least aportion of the support structure to provide a cushion between the atleast a portion of the support structure and the leaflet.
 60. The valveof claim 56, wherein the support structure includes a first end and asecond end opposite the first end, the second end comprising a pluralityof posts extending longitudinally therefrom, wherein the cushion memberis wrapped about each post to provide a cushion between the post and aportion of the leaflet coupled to at least a portion of the post. 61.The valve of claim 32, wherein the support structure is selectivelydiametrically adjustable for endovascular delivery and deployment at atreatment site.
 62. The valve of claim 32, wherein the compositematerial comprises at least one layer of the synthetic polymer membrane,wherein the at least one synthetic polymer membrane is expandedfluoropolymer membrane, and wherein the elastomer is a TFE/PMVEcopolymer.
 63. The valve of claim 32, wherein the composite materialcomprises at least one layer of the synthetic polymer membrane, whereinthe at least one synthetic polymer membrane is porous polyethylenemembrane, and wherein the elastomer is a silicone.
 64. A valve,comprising: a support structure, and at least one leaflet beingsupported on the support structure and movable between open and closedpositions, each leaflet including a composite material comprising atleast one synthetic polymer membrane and an elastomer, the at least onesynthetic polymer membrane comprising fibers that define spacetherebetween, the space between the fibers defining pores that have apore size that is less than about 5 μm, the elastomer being disposed insubstantially all of the pores.
 65. The valve of claim 64, wherein thecomposite material further includes a layer of an elastomer.
 66. Thevalve of claim 64, wherein the at least one synthetic polymer membraneis fluoropolymer membrane.
 67. The valve of claim 64, wherein the atleast one synthetic polymer membrane is porous polyethylene membrane.68. The valve of claim 64, wherein the elastomer is silicone.
 69. Thevalve of claim 64, wherein the elastomer is a fluoroelastomer.
 70. Thevalve of claim 64, wherein the elastomer is a urethane.
 71. The valve ofclaim 64, wherein the elastomer is a TFE/PMVE copolymer.
 72. The valveof claim 71, wherein the TFE/PMVE copolymer comprises essentially ofbetween about 40 and 80 weight percent perfluoromethyl vinyl ether andcomplementally 60 and 20 weight percent tetrafluoroethylene.
 73. Thevalve of claim 67, wherein the porous polyethylene membrane has a matrixtensile strength in at least one direction greater than about 150 MPa.74. The valve of claim 64, wherein the leaflet has a thickness of lessthan about 350 μm.
 75. The valve of claim 64, wherein the compositematerial comprises at least one layer of the synthetic polymer membrane.76. The valve of claim 64, wherein the composite material comprises morethan two layers of the synthetic polymer membrane.
 77. The valve ofclaim 76, wherein the leaflet comprises overlapping wrappings of thecomposite material, wherein the layers of the synthetic polymer membraneare defined by a number of overlapping wrappings of the compositematerial.
 78. The valve of claim 67, wherein the leaflet has a ratio ofleaflet thickness (μm) to number of layers of synthetic polymer membraneof less than about
 20. 79. The valve of claim 64, wherein the supportstructure is selectively diametrically adjustable for endovasculardelivery and deployment at a treatment site, wherein the valve isoperable to be a prosthetic heart valve.
 80. The valve of claim 64,wherein a diameter of a majority of the fibers is less than about 1 μm.81. The valve of claim 64, wherein a diameter of a majority of thefibers is less than about 0.1 μm.
 82. The valve of claim 64, wherein thepores have a pore size that is less than about 1 μm.
 83. The valve ofclaim 64, wherein the pores have a pore size that is less than about0.10 μm.
 84. The valve of claim 64, wherein the at least one syntheticpolymer membrane comprises substantially only of fibers.
 85. The valveof claim 64, wherein the composite material comprises elastomer byweight in a range from about 10% to about 90%.
 86. The valve of claim75, wherein the leaflet has a ratio of leaflet thickness (μm) to numberof layers of synthetic polymer membrane of less than about
 20. 87. Thevalve of claim 75, wherein the leaflet has at least 10 layers of porouspolyethylene membrane and the composite material comprising less thanabout 50% synthetic polyethylene membrane by weight.
 88. The valve ofclaim 64, further comprising: a cushion member located between at leasta portion of the support structure and at least a portion of theleaflet, wherein the cushion member comprises a second compositematerial with at least one synthetic polymer membrane having a pluralityof pores and an elastomer present in substantially all of the pores. 89.The valve of claim 88, wherein the cushion member includes porouspolyethylene membrane.
 90. The valve of claim 88, wherein the cushionmember at least partially covers the at least a portion of the supportstructure to provide a cushion between the at least a portion of thesupport structure and the leaflet.
 91. The valve of claim 88, whereinthe cushion member is wrapped about the at least a portion of thesupport structure to provide a cushion between the at least a portion ofthe support structure and the leaflet.
 92. The valve of claim 88,wherein the support structure includes a first end and a second endopposite the first end, the second end comprising a plurality of postsextending longitudinally therefrom, wherein the cushion member iswrapped about each post to provide a cushion between the post and aportion of the leaflet coupled to at least a portion of the post. 93.The valve of claim 64, wherein the composite material comprises at leastone layer of the synthetic polymer membrane, wherein the at least onesynthetic polymer membrane is expanded fluoropolymer membrane, whereinthe elastomer is a TFE/PMVE copolymer, and wherein the valve is operableto be a prosthetic heart valve.
 94. The valve of claim 64, wherein thecomposite material comprises at least one layer of the synthetic polymermembrane, wherein the at least one synthetic polymer membrane is porouspolyethylene membrane, wherein the elastomer is a silicone, and whereinthe valve is operable to be a prosthetic heart valve.
 95. A method offorming a leaflet of a prosthetic heart valve, the method comprising:providing a composite material comprising at least one synthetic polymermembrane and an elastomer, the at least one synthetic polymer membranecomprising fibers that define space therebetween, wherein a diameter ofa majority of the fibers is less than about 1 μm, the space between thefibers defining pores, the elastomer being disposed in substantially allof the pores; bringing more than one layer of the composite materialinto contact with additional layers of the composite material; andbonding the layers of composite material together.
 96. The method offorming a leaflet of a prosthetic heart valve of claim 95, whereinproviding the at least one synthetic polymer membrane comprisesproviding expanded fluoropolymer membrane, and wherein providing theelastomer comprises providing a TFE/PMVE copolymer.
 97. The method offorming a leaflet of a prosthetic heart valve of claim 95, whereinproviding the at least one synthetic polymer membrane comprisesproviding porous polyethylene membrane, and wherein providing theelastomer comprises providing silicone.
 98. A method of forming aprosthetic heart valve, comprising: providing a generally annularsupport structure; providing a composite material comprising at leastone synthetic polymer membrane and an elastomer, the at least onesynthetic polymer membrane comprising fibers that define spacetherebetween, wherein a diameter of a majority of the fibers is lessthan about 1 μm, the space between the fibers defining pores, theelastomer being disposed in substantially all of the pores; wrapping thecomposite material about the support structure bringing more than onelayer of the composite material into contact with additional layers ofthe composite material; and bonding the layers of composite material toitself and to the support structure so as to define leaflets.
 99. Themethod of forming a prosthetic heart valve of claim 98, whereinproviding a generally annular support structure comprises providing agenerally annular support structure having a first end and a second endopposite the first end, the second end comprising a plurality of postsextending longitudinally therefrom, wherein wrapping the compositematerial about the support structure comprises wrapping the compositematerial from post to post wherein the leaflets are defined by thecomposite material that is between the posts.
 100. The method of forminga prosthetic heart valve of claim 99, further comprising: wrapping acushion member about each post to provide a cushion between the post anda portion of the leaflet coupled to at least a portion of the post,wherein the cushion member comprises a second composite material with atleast one synthetic polymer membrane comprising fibers that define spacetherebetween, wherein a diameter of a majority of the fibers is lessthan about 1 μm, the space between the fibers defining pores and anelastomer present in substantially all of the pores.
 101. The method offorming a prosthetic heart valve of claim 98, wherein providing the atleast one synthetic polymer membrane comprises providing expandedfluoropolymer membrane, and wherein providing the elastomer comprisesproviding a TFE/PMVE copolymer.
 102. The method of forming a prostheticheart valve of claim 98, wherein providing the at least one syntheticpolymer membrane comprises providing porous polyethylene membrane, andwherein providing the elastomer comprises providing silicone.
 103. Amethod of forming a leaflet of a prosthetic heart valve, the methodcomprising: providing a composite material comprising at least onesynthetic polymer membrane and an elastomer, the at least one syntheticpolymer membrane comprising fibers that define space therebetween, thespace between the fibers defining pores that have a pore size of lessthan about 5 μm, the elastomer being disposed in substantially all ofthe pores; bringing more than one layer of the composite material intocontact with additional layers of the composite material; and bondingthe layers of composite material together.
 104. The method of forming aleaflet of a prosthetic heart valve of claim 103, wherein providing theat least one synthetic polymer membrane comprises providing expandedfluoropolymer membrane, and wherein providing the elastomer comprisesproviding a TFE/PMVE copolymer.
 105. The method of forming a leaflet ofa prosthetic heart valve of claim 106, wherein providing the at leastone synthetic polymer membrane comprises providing porous polyethylenemembrane, and wherein providing the elastomer comprises providingsilicone.
 106. A method of forming a prosthetic heart valve, comprising:providing a generally annular support structure; providing a compositematerial comprising at least one synthetic polymer membrane and anelastomer, the at least one synthetic polymer membrane comprising fibersthat define space therebetween, the space between the fibers definingpores that have a pore size of less than about 5 μm, the elastomer beingdisposed in substantially all of the pores; wrapping the compositematerial about the support structure bringing more than one layer of thecomposite material into contact with additional layers of the compositematerial; and bonding the layers of composite material to itself and tothe support structure so as to define leaflets.
 107. The method offorming a prosthetic heart valve of claim 106, wherein providing agenerally annular support structure comprises providing a generallyannular support structure having a first end and a second end oppositethe first end, the second end comprising a plurality of posts extendinglongitudinally therefrom, wherein wrapping the composite material aboutthe support structure comprises wrapping the composite material frompost to post wherein the leaflets are defined by the composite materialthat is between the posts.
 108. The method of forming a prosthetic heartvalve of claim 107, further comprising: wrapping a cushion member abouteach post to provide a cushion between the post and a portion of theleaflet coupled to at least a portion of the post, wherein the cushionmember comprises a second composite material with at least one syntheticpolymer membrane comprising fibers that define space therebetween,wherein a diameter of a majority of the fibers is less than about 1 μm,the space between the fibers defining pores and an elastomer present insubstantially all of the pores.
 109. The method of forming a prostheticheart valve of claim 106, wherein providing the at least one syntheticpolymer membrane comprises providing expanded fluoropolymer membrane,and wherein providing the elastomer comprises providing a TFE/PMVEcopolymer.
 110. The method of forming a prosthetic heart valve of claim106, wherein providing the at least one synthetic polymer membranecomprises providing porous polyethylene membrane, and wherein providingthe elastomer comprises providing silicone.